Clusterin: A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Complement Inactivator Proteins: Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.Rete Testis: The network of channels formed at the termination of the straight SEMINIFEROUS TUBULES in the mediastinum testis. Rete testis channels drain into the efferent ductules that pass into the caput EPIDIDYMIS.SwedenSoftware: Sequential operating programs and data which instruct the functioning of a digital computer.User-Computer Interface: The portion of an interactive computer program that issues messages to and receives commands from a user.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Word Processing: Text editing and storage functions using computer software.Computer Graphics: The process of pictorial communication, between human and computers, in which the computer input and output have the form of charts, drawings, or other appropriate pictorial representation.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Sialic Acids: A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.Carbohydrates: The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Mammaglobin B: A MAMMAGLOBIN A-related secretoglobin that is expressed in several HUMAN tissues including the UTERUS; BREAST; SALIVARY GLAND; and LACRIMAL GLAND.Toremifene: A first generation selective estrogen receptor modulator (SERM). Like TAMOXIFEN, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue.Estrogen Receptor Modulators: Substances that possess antiestrogenic actions but can also produce estrogenic effects as well. They act as complete or partial agonist or as antagonist. They can be either steroidal or nonsteroidal in structure.Tamoxifen: One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.Breast Neoplasms: Tumors or cancer of the human BREAST.Neoadjuvant Therapy: Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment.Stem Cell Research: Experimentation on STEM CELLS and on the use of stem cells.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Inclusion Bodies: A generic term for any circumscribed mass of foreign (e.g., lead or viruses) or metabolically inactive materials (e.g., ceroid or MALLORY BODIES), within the cytoplasm or nucleus of a cell. Inclusion bodies are in cells infected with certain filtrable viruses, observed especially in nerve, epithelial, or endothelial cells. (Stedman, 25th ed)Vimentin: An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000.ArchivesBiological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Directories as Topic: Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)

Recovery following relief of unilateral ureteral obstruction in the neonatal rat. (1/535)

BACKGROUND: Obstructive nephropathy is a primary cause of renal insufficiency in infants and children. This study was designed to distinguish the reversible and irreversible cellular consequences of temporary unilateral ureteral obstruction (UUO) on the developing kidney. METHODS: Rats were subjected to UUO or sham operation in the first 48 hours of life, and the obstruction was removed five days later (or was left in place). Kidneys were removed for study 14 or 28 days later. In additional groups, kidneys were removed at the end of five days of obstruction. Immunoreactive distribution of renin was determined in arterioles, and the distribution of epidermal growth factor, transforming growth factor-beta1, clusterin, vimentin, and alpha-smooth muscle actin was determined in tubules and/or interstitium. The number of glomeruli, glomerular maturation, tubular atrophy, and interstitial collagen deposition was determined by morphometry. Renal cellular proliferation and apoptosis were measured by proliferating cell nuclear antigen and the TdT uridine-nick-end-label technique, respectively. The glomerular filtration rate was measured by inulin clearance. RESULTS: Renal microvascular renin maintained a fetal distribution with persistent UUO; this was partially reversed by the relief of obstruction. Although glomerular maturation was also delayed and glomerular volume was reduced by UUO, the relief of obstruction prevented the reduction in glomerular volume. Although relief of obstruction did not reverse a 40% reduction in the number of nephrons, the glomerular filtration rate of the postobstructed kidney was normal. The relief of obstruction did not improve tubular cell proliferation and only partially reduced apoptosis induced by UUO. This was associated with a persistent reduction in the tubular epidermal growth factor. In addition, the relief of obstruction reduced but did not normalize tubular expression of transforming growth factor-beta1, clusterin, and vimentin, all of which are evidence of persistent tubular injury. The relief of obstruction significantly reduced interstitial fibrosis and expression of alpha-smooth muscle actin by interstitial fibroblasts, but not to normal levels. CONCLUSIONS: The relief of obstruction in the neonatal rat attenuates, but does not reverse, renal vascular, glomerular, tubular, and interstitial injury resulting from five days of UUO. Hyperfiltration by remaining nephrons and residual tubulointerstitial injury in the postobstructed kidney are likely to lead to deterioration of renal function later in life.  (+info)

Clusterin has chaperone-like activity similar to that of small heat shock proteins. (2/535)

Clusterin is a highly conserved protein which is expressed at increased levels by many cell types in response to a broad variety of stress conditions. A genuine physiological function for clusterin has not yet been established. The results presented here demonstrate for the first time that clusterin has chaperone-like activity. At physiological concentrations, clusterin potently protected glutathione S-transferase and catalase from heat-induced precipitation and alpha-lactalbumin and bovine serum albumin from precipitation induced by reduction with dithiothreitol. Enzyme-linked immunosorbent assay data showed that clusterin bound preferentially to heat-stressed glutathione S-transferase and to dithiothreitol-treated bovine serum albumin and alpha-lactalbumin. Size exclusion chromatography and SDS-polyacrylamide gel electrophoresis analyses showed that clusterin formed high molecular weight complexes (HMW) with all four proteins tested. Small heat shock proteins (sHSP) also act in this way to prevent protein precipitation and protect cells from heat and other stresses. The stoichiometric subunit molar ratios of clusterin:stressed protein during formation of HMW complexes (which for the four proteins tested ranged from 1.0:1.3 to 1.0:11) is less than the reported ratios for sHSP-mediated formation of HMW complexes (1.0:1.0 or greater), indicating that clusterin is a very efficient chaperone. Our results suggest that clusterin may play a sHSP-like role in cytoprotection.  (+info)

Clusterin gene expression mediates resistance to apoptotic cell death induced by heat shock and oxidative stress. (3/535)

Clusterin is a widely expressed, well conserved, secreted glycoprotein, which is highly induced in tissues regressing as a consequence of apoptotic cell death in vivo. It has recently been shown that clusterin expression is only confined to surviving cells following the induction of apoptosis in vitro, suggesting that it is involved in cell survival rather than death. In the hypothesis that clusterin may be implicated in cellular responses to stress, clusterin gene expression was analyzed in the A431 human epidermoid cancer cell line following heat shock and oxidative stress. Our results show that both a transient heat shock (20 min at 42 degrees C) and various oxidative stresses, including hydrogen peroxide, superoxide anion, hyperoxia and UVA exposure, induce a strong increase in clusterin mRNA levels as assessed by northern blot. Nuclear run-on analysis suggests that transcriptional activation is involved in inducing clusterin mRNA in response to heat shock. Using pulse-chase analysis of control and heat shocked cells, it is shown that clusterin mRNA is translated and secreted, thus resulting in increased extracellular levels of the protein following heat shock. To investigate the function of clusterin in response to these stresses, clusterin anti-sense transfectants that stably express virtually no clusterin at the mRNA and protein level were generated in A431 cells. These anti-sense transfectants are shown to be highly sensitive to apoptotic cell death induced by heat shock or oxidative stress compared with wild-type A431 cells or control transfectants. Taken together, our results show that clusterin gene expression is induced in response to heat shock and oxidative stress in human A431 cells, and confers cellular protection against heat shock and oxidative stress.  (+info)

Effect of targeted expression of clusterin in photoreceptor cells on retinal development and differentiation. (4/535)

Clusterin expression is increased in tissues undergoing apoptosis, including neurodegenerative retina, but the causal relationships remain to be clarified. To test the hypothesis that overexpression of clusterin could induce apoptosis in neurons, transgenic mice were generated in which rat clusterin transgene was expressed in photoreceptor cells under the transcriptional control of the human interphotoreceptor retinoid-binding protein (IRBP) promoter. Photoreceptor cell death in the resulting transgenic mice was examined by histology and TUNEL techniques. The expression of the clusterin transgene was confirmed by in situ hybridization in the photoreceptor cells, and results in a complex pattern of clusterin protein distribution in the retina. A reduction in apoptotic staining in the transgenic retinas was observed from birth to postnatal day 15. These results suggest that clusterin is not causally involved in apoptotic mechanisms of photoreceptor cell death, but may relate to cytoprotective functions.  (+info)

Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells. (5/535)

Clusterin (apolipoprotein J) is an extracellular glycoprotein that might exert functions in development, cell death and lipid transport. Clusterin gene expression is elevated at sites of tissue remodelling, such as differentiation and apoptosis; however, the signals responsible for this regulation have not been identified. We use here the clusterin gene as a model system to examine expression in PC12 cells under the control of differentiation and proliferation signals produced by nerve growth factor (NGF) and by epidermal growth factor (EGF) respectively. NGF induced clusterin mRNA, which preceded neurite outgrowth typical of neuronal differentiation. EGF also activated the clusterin mRNA, demonstrating that both proliferation and differentiation signals regulate the gene. To localize NGF- and EGF-responsive elements we isolated the clusterin promoter and tested it in PC12 cell transfections. A 2.5 kb promoter fragment and two 1.5 and 0.3 kb deletion mutants were inducible by NGF and EGF. The contribution to this response of a conserved activator protein 1 (AP-1) motif located in the 0.3 kb fragment was analysed by mutagenesis. The mutant promoter was not inducible by NGF or EGF, which identifies the AP-1 motif as an element responding to both factors. Binding studies with PC12 nuclear extracts showed that AP-1 binds to this sequence in the clusterin promoter. These findings suggest that NGF and EGF, which give differential gene regulation in PC12 cells, resulting in neuronal differentiation and proliferation respectively, use the common Ras/extracellular signal-regulated kinase/AP-1 signalling pathway to activate clusterin expression.  (+info)

Clusterin (SGP-2) gene expression is cell cycle dependent in normal human dermal fibroblasts. (6/535)

In confluent human dermal fibroblasts brought to quiescence (G0) by serum starvation, the S phase peaked at 24 h after serum re-addiction and G2/M phase peaked at 36 h. This was confirmed by titration of h-gas1 mRNA (a marker of G0 phase) and histone H3 (a marker of S phase). Clusterin mRNA accumulation progressively increased in cells proceeding to confluence after seeding and to quiescence upon serum starvation, and peaked at around G0, in parallel with h-gas1 mRNA. At 6 h (roughly G1 phase) clusterin transcript formed a second peak, followed by a gradual decrease until 36 h. Correspondence of clusterin protein accumulation to its mRNA occurred solely with regard to the G0 peak but not to the second one. The possible meaning of the cell cycle related clusterin gene expression is discussed.  (+info)

Isolation of Ku70-binding proteins (KUBs). (7/535)

DNA-dependent protein kinase (DNA-PK) plays a critical role in resealing DNA double-stand breaks by non-homologous end joining. Aside from DNA-PK, XRCC4 and DNA ligase IV, other proteins which play a role(s) in this repair pathway remain unknown; DNA-PK contains a catalytic subunit (DNA-PKcs) and a DNA binding subunit (Ku70 and Ku80). We isolated Ku70-binding proteins (KUB1-KUB4) using yeast two-hybrid analyses. Sequence analyses revealed KUB1 to be apolipoprotein J (apoJ), also known as X-ray-inducible transcript 8 (XIP8), testosterone-repressed prostate message-2 (TRPM-2) and clusterin. KUB2 is Ku80. KUB3 and KUB4 are unknown, >10 kb trans-cripts. Interactions of apoJ/XIP8 or KUB3 with Ku70 were confirmed by co-immunoprecipitation analyses in MCF-7:WS8 breast cancer or IMR-90 normal lung fibroblast cells, respectively. The interaction of apoJ/XIP8 with Ku70 was confirmed by far-western analyses. Stable over-expression of full-length apoJ/XIP8 in MCF-7:WS8 caused decreased Ku70/Ku80 DNA end binding that was restored by apoJ/XIP8 monoclonal antibodies. The role of apoJ/XIP8 in ionizing radiation resistance/sensitivity is under investigation.  (+info)

Targeted disruption of the murine lecithin:cholesterol acyltransferase gene is associated with reductions in plasma paraoxonase and platelet-activating factor acetylhydrolase activities but not in apolipoprotein J concentration. (8/535)

Lecithin:cholesteryl acyltransferase (LCAT) deficiency resulting from targeted disruption of the Lcat gene in the mouse is associated with dramatic decreases in HDL concentration and the accumulation of nascent HDL in the plasma. We examined whether LCAT deficiency in mice is associated with a concomitant decrease in two antioxidative enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH). In control Lcat (+/+) mice both these enzymes are transported on HDL. Compared to Lcat (+/+) mice, HDL-cholesterol is reduced 94% and apoA-I, 90%, in Lcat (-/-) mice; this reduction in HDL is paralleled by a 71% decrease in PAF-AH activity and in a 58% decrease in PON activity. Apolipoprotein J (apoJ) levels, rather than being decreased, were significantly (P = 0.01) higher (36%) in Lcat (-/-) than in Lcat (+/+) mice, and the apo J/PON ratio was 3-fold greater in Lcat (-/-) than in Lcat (+/+) animals. Even though apolipoprotein A-I (apoA-I) concentration and PON activity were drastically reduced, there was no reduction in apoA-I and PON liver mRNA levels suggesting that post-transcriptional events are responsible for the reduction of plasma PON and apoA-I levels. Fast protein liquid chromatography (FPLC) revealed that in Lcat (+/+) mice both PON and PAF-AH activity is associated with large, apoA-I-containing HDL particles (9.7 nm by non-denaturing gradient gel electrophoresis) while in Lcat (-/-) mice both enzymes are associated with small 8.2 nm particles. We conclude that the concomitant reduction in HDL and apoA-I concentrations and PON and PAF-AH activities is best explained by rapid clearance of the small HDL particles found in LCAT deficiency.  (+info)

  • After it was first demonstrated that folic acid increased renal clusterin mRNA in the rat, a species in which renal clusterin was highly inducible by other stimuli, the effects of folic acid (250 mg/kg ip) on clusterin mRNA and immunoreactivity were examined in mice sufficient and deficient for the fifth component of complement. (elsevier.com)
  • Similar increases in clusterin mRNA and immunoreactivity were seen in both the C5-sufficient and C5-deficient mice compared with their respective vehicle-injected control groups. (elsevier.com)
  • Renal clusterin mRNA was also increased to a similar extent in the remaining kidney of both C5-sufficient and C5-deficient mice 10 days after subtotal nephrectomy. (elsevier.com)
  • The authors examined the pattern of clusterin mRNA expression in the developing rat embryo and found it not to correlate with regions undergoing developmental cell death. (mussenhealth.us)
  • The fact that nearly every neuron in the adult forebrain was positive for clusterin mRNA made it unlikely that clusterin correlated with programmed cell death in the majority of cells expressing it. (mussenhealth.us)
  • To further explore the interaction between Clusterin and complement, the requirement for an intact complement system for renal Clusterin induction in an acute (folic acid nephropathy) and a chronic (subtotal renal ablation) model of renal injury was examined. (elsevier.com)
  • In conclusion, the induction of clusterin after folic acid administration or subtotal nephrectomy was independent of the presence of an intact complement system, because similar increases in clusterin expression were observed in C5-sufficient and C5-deficient mice. (elsevier.com)
  • In the latter study, virtually all neurons were shown to be clusterin-positive by immunohistochemistry . (mussenhealth.us)
  • Rather, they found increasing clusterin message to be associated with neuronal differentiation. (mussenhealth.us)
  • Consistent with these data and supportive of a role for clusterin in the maturation of the nervous tissue are the observations made by O'Bryan et al33 during neuronal development in the mouse. (mussenhealth.us)
  • We attempted to verify in an experimental model the role of cytoplasmic clusterin (CLU), a cytoprotective protein found to be up-regulated in antiestrogen-resistant patients, following neoadjuvant treatment with toremifene. (spandidos-publications.com)
  • Resistant cells were characterised by higher levels of cytoplasmic clusterin than sensitive cells, and antiestrogen treatments up-regulated clusterin levels in both sensitive and resistant cell lines. (spandidos-publications.com)
  • We therefore concluded that: i) basal clusterin levels are higher in antiestrogen resistant cells, ii) clusterin is up-regulated following antiestrogen treatment independently of the sensitivity of the cell line, iii) down-regulation of cytoplasmic clusterin restores sensitivity to toremifene in the antiestrogen-resistant cell line. (spandidos-publications.com)
  • A direct role for clusterin in programmed cell death in the rat CNS was subsequently disclosed in a study by Garden and coworkers32 using in situ hybridization. (mussenhealth.us)
  • Human native Clusterin was filtered (0.4µm) and lyophilized from 0.5mg/ml in 0.1M phosphate buffer, 0.15M NaCl pH 7.5. (prospecbio.com)
  • The role of cytoplasmic clusterin in modulating response to two antiestrogens (toremifene and tamoxifen) was studied in two ER+ anti-estrogen-sensitive cell lines (MCF-7, 734B) and one ER+ antiestrogen-resistant cell line (T47D) using siRNA strategy. (spandidos-publications.com)
  • Apolipoprotein J/clusterin (apoJ/clusterin), an intriguing protein with unknown function, is induced in myocarditis and numerous other inflammatory injuries. (jci.org)
  • Immunohistochemistry-Paraffin: APOJ / Clusterin Antibody [NBP1-- Staining of human tonsil shows strong positivity in squamous epithelial cells. (novusbio.com)
  • Apoliprotein J (apoJ)/clusterin has attracted considerable interest based on its inducibility in multiple injury processes and accumulation at sites of remodeling, regression, and degeneration. (asm.org)
  • Aging mice deficient in apoJ/clusterin developed a progressive glomerulopathy characterized by the deposition of immune complexes in the mesangium. (asm.org)
  • Up to 75% of glomeruli in apoJ/clusterin-deficient mice exhibited moderate to severe mesangial lesions by 21 months of age. (asm.org)
  • In the apoJ/clusterin-deficient mice, immune complexes of immunoglobulin G (IgG), IgM, IgA, and in some cases C1q, C3, and C9 were detectable as early as 4 weeks of age. (asm.org)
  • In young apoJ/clusterin-deficient animals, the development of immune complex lesions was accelerated by unilateral nephrectomy-induced hyperfiltration. (asm.org)
  • Injected immune complexes localized to the mesangium of apoJ/clusterin-deficient but not wild-type mice. (asm.org)
  • These results establish a protective role of apoJ/clusterin against chronic glomerular kidney disease and support the hypothesis that apoJ/clusterin modifies immune complex metabolism and disposal. (asm.org)
  • Newkirk MM, Apostolakos P, Neville C and Fortin PR: Systemic lupus erythematosus, a disease associated with low levels of Clusterin/ApoJ, and anti-inflammatory protein. (biovendor.com)
  • Clusterin/apolipoprotein J (apoJ) is an extracellular chaperone involved in the quality control system against protein aggregation. (sigmaaldrich.com)
  • Clusterin, also known as complement-associated protein SP-4, Complement cytolysis inhibitor, Apolipoprotein J, Testosterone-repressed prostate message 2, Aging-associated gene 4 protein, CLU and APOJ, is a secreted protein which belongs to the clusterin family. (sinobiological.com)
  • Michel D, Chatelanin G, North S, Brun G. Stress-induced transcription of the clusterin/apoJ gene. (koreascience.or.kr)
  • Clusterin, also known as apolipoprotein J (apoJ), is one of the most abundantly expressed apolipoproteins in the brain after apolipoprotein E (apoE). (beds.ac.uk)
  • Clusterin is involved in several biological processes including extra- and intracellular chaperone activity, pro- and anti-apoptotic properties, lipid transportation, cell clustering, modulation of NF-kappa-B transcriptional activity, and complement inhibition. (biolegend.com)
  • Clusterin protects neurons against intracellular proteotoxicity" by Jenna Gregory, Daniel Whiten et al. (edu.au)
  • We have examined in this study whether or not increased expression of clusterin is able to protect neuronal cells against intracellular protein aggregation and cytotoxicity, characteristics that are strongly implicated in a range of neurodegenerative diseases. (edu.au)
  • We therefore conclude that increased expression of clusterin can provide an important defense against intracellular proteotoxicity under conditions that mimic specific features of neurodegenerative disease. (edu.au)
  • We studied the biological effects of intracellular clusterin and observed that clusterin forms containing the α-chain region strongly accumulated in an ubiquitinated form in juxtanuclear aggregates meeting the main criterions of aggresomes and leading to profound alterations of the mitochondrial network. (biologists.org)
  • The viability of cells transfected by intracellular forms of clusterin was improved by overexpression of Bcl-2, and caspase inhibition was capable of rescuing cells expressing clusterin, which presented an altered mitochondrial permeability. (biologists.org)
  • We propose that, although it might be an inherently pro-survival and anti-apoptotic protein expressed by cells under stress in an attempt to protect themselves, clusterin can become highly cytotoxic when accumulated in the intracellular compartment. (biologists.org)
  • Antibodies to all four proteins showed staining of dystrophic neurites and neuropil threads in AD tissue, and residual serum in normal tissue, but only antibodies to clusterin and vitronectin strongly stained amyloid deposits in senile plaques. (nih.gov)
  • Clusterin, vitronectin and protectin are all believed to inhibit membrane insertion by the MAC, and these data are consistent with upregulation of all three proteins in response to MAC formation in AD, and with a neuronal origin of clusterin. (nih.gov)
  • The only member common to both lists-which contained eight proteins apiece, many of them inflammatory factors involved in the complement system-was clusterin, an extracellular chaperone that regulates amyloid formation and clearance. (alzforum.org)
  • They find that clusterin can accumulate in juxtanuclear aggregates that exhibit features characteristic of aggresomes (inclusion bodies thought to prevent misfolded proteins spreading throughout the cell). (biologists.org)
  • Clusterin is a protein that occurs naturally in tears and acts to protect cells and proteins. (visivite.com)
  • Clusterin forms complexes with C5b:C6:C7, or C5b:C6:C7:C8 or C5b:C6:C7:C8:C9, as the proteins assemble into the amphiphilic MAC. (reactome.org)
  • The levels of clusterin proteins and mRNA in the tissues were measured by immunohistochemistry and Northern blot analyses, respectively. (koreascience.or.kr)
  • Clusterin/apo J, a multifunctional secreted chaperone, is one of the major proteins accumulating in drusen deposits. (meta.org)
  • CONCLUSIONS: These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD. (ox.ac.uk)
  • Laure Debure and co-workers have examined the effects of clusterin expression in COS-7 cells (see p. 3109 ). (biologists.org)
  • We used the amyotrophic lateral sclerosis-associated protein TDP-43 as a primary model to investigate the effects of clusterin on protein aggregation and neurotoxicity in complementary in vitro, neuronal cell and Drosophila systems. (edu.au)
  • The present study, led by Dr. Martin Gleave and published in EMBO Molecular Medicine http://onlinelibrary.wiley.com/doi/10.15252/emmm.201506059/full (May 2016), explored the biological effects of clusterin (CLU) on mitosis, finding that silencing CLU-induced activation of Cdc25C makes cancer cells more sensitive to mitotic-targeting agents such as chemotherapy. (tfri.ca)
  • We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. (biomedcentral.com)
  • BOTHELL, Wash. and VANCOUVER, British Columbia , Sept. 28, 2015 /CNW/ -- OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today results from additional exploratory analyses of the Phase 3 SYNERGY trial demonstrating that custirsen treatment significantly lowered serum clusterin (sCLU) levels from baseline in men with metastatic castrate-resistant prostate cancer (mCRPC). (newswire.ca)
  • These data support that custirsen is inhibiting the production of clusterin in men with metastatic CRPC and a correlation between treatment-induced reductions in sCLU and clinical benefit in those patients at risk for poor outcomes,' said Scott Cormack , President and CEO of OncoGenex. (newswire.ca)
  • Secretory clusterin (sCLU) is a cytoprotective protein that guards against genotoxic stresses. (aacrjournals.org)
  • In prostate cancer the secreted form of clusterin (sCLU) has been described as an anti-apoptotic protein whose expression is increased after therapeutic intervention, whereas, the nuclear protein form nCLU was reported to have pro-apoptotic properties. (plos.org)
  • ATM regulates insulin-like growth factor 1-secretory clusterin (IGF-1-sCLU) expression that protects cells against senescence. (telomerescience.com)
  • Lipocalin 2, clusterin, soluble tumor necrosis factor receptor-1 (sTNFR-1), interleukin-6, homocysteine, and uric acid are inflammatory and/or biochemical markers. (hindawi.com)
  • Production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. (newswire.ca)
  • Here, clusterin (CLU) was identified as a novel target gene of DEC1 and suppresses DNA damage-induced cell death in tumor cells. (aacrjournals.org)
  • To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU) that over-expresses clusterin. (biomedcentral.com)
  • Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. (biomedcentral.com)
  • These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells. (biomedcentral.com)
  • Induction of clusterin by AKT--role in cytoprotection against docetaxel in prostate tumor cells. (semanticscholar.org)
  • The i.v. administration of Pc 4 to mice bearing chemically or UVB radiation-induced skin papillomas, followed by light application, led to increased clusterin protein expression, peaking 24 h after the treatment, when tumor regression was apparently visible. (elsevier.com)
  • These data, for the first time, demonstrate the involvement of clusterin in PDT-mediated cell death and during tumor regression. (elsevier.com)
  • During a study spanning nearly a decade, researchers at The Ohio State University College of Medicine, Houston Methodist Research Institute and Houston Methodist Cancer Center have linked the protein clusterin - for the first time -- to many different facets of cardiometabolic syndrome risk through its actions in the liver. (news-medical.net)
  • Our objective was to determine 1 ) whether subcutaneous AT adipocyte (SAd) clusterin and serum clusterin are associated with insulin resistance (IR) and known markers of cardiometabolic risk and 2 ) how clusterin may contribute to increased risk. (diabetesjournals.org)
  • The aim of this study was to investigate serum levels of lipocalin 2, clusterin, sTNFR-1, interleukin-6, homocysteine, and uric acid in patients and controls groups. (hindawi.com)
  • Morrissey C, Lakins J, Moquin A, Hussain M, Tenniswood M: An antigen capture assay for the measurement of serum Clusterin concentrations. (biovendor.com)
  • Native clusterin purified from human serum. (anacrom.com)
  • Although there are many factors regarding multiple resistance that are still unknown, studies show that it may be mediated by different mechanisms, one of which is closely related to the expression of the clusterin (CLU) protein ( 2, 3 ). (aacrjournals.org)
  • Whether clusterin turns out to be a useful biomarker remains to be seen, but the new data lend credence to the idea that the protein may play some role in AD pathogenesis. (alzforum.org)
  • Suppression of clusterin with antisense oligonucleotide induced growth arrest, whereas transient overexpression of clusterin by cDNA transfection or exogenous treatment with purified clusterin promoted proliferation of the primary astrocytes in culture. (elsevier.com)
  • According to the findings of a community-based study, in younger patients higher clusterin levels involved a ________ risk of Alzheimer disease (AD) and __________ risk of stroke. (mdedge.com)
  • Clusterin is a protein of 449 amino acids with a molecular mass of 52 kD. (biolegend.com)
  • Western analysis revealed that two major groups of clusterin exist in the eye, a high molecular weight group (>100 kDa) and a second group consisting of at least five clusterin species that are all approximately 80 kDa. (edu.au)
  • Meanwhile, the molecular size of clusterin mRNA detected in the array of tissues are identical in size, suggesting that the nature of the diversity in clusterin forms is due to post-translational modifications. (edu.au)
  • Gentaur Molecular :Biovend \ Clusterin Rec. (antibody-antibodies.com)
  • Clusterin Canine Recombinant produced in HEK293 cells is a single, glycosylated, Polypeptide chain containing 436 amino acids and having a molecular mass of 50.72 kDa. (promab.com)
  • Clusterin purified from human platelets had the same molecular weight as plasma clusterin under nonreducing conditions and was composed of two disulfide-linked nonidentical subunits of the same size. (ashpublications.org)
  • In the first, Simon Lovestone, King's College London, and colleagues report in this month's Archives of General Psychiatry that plasma levels of clusterin track with AD severity, pathology, and clinical progression. (alzforum.org)
  • In the expanded cohort, Lovestone's team found that those with higher plasma clusterin levels had greater atrophy in the entorhinal cortex, more amyloid in the medial temporal lobe, and poorer performance on the Mini-Mental State Examination. (alzforum.org)
  • Proteomic analysis of plasma from the REVE-2 study (Remodelage Ventriculaire)-a study dedicated to the analysis of LVR which included 246 patients after a first anterior myocardial infarction-identified increased plasma levels of CLU (clusterin) in patients with high LVR. (nih.gov)
  • Plasma clusterin was reported to be associated with brain atrophy, baseline disease severity, and rapid clinical progression in patients with AD. (eur.nl)
  • Objective: To evaluate the potential of plasma clusterin as a biomarker of the presence, severity, and risk of AD. (eur.nl)
  • Plasma levels of clusterin were measured at baseline (1997-1999) in 60 individuals with prevalent AD, a random subcohort of 926 participants, and an additional 156 participants diagnosed with AD during follow-up until January 1, 2007 (mean [SD], 7.2 [2.years). (eur.nl)
  • Conclusion: Plasma clusterin levels were significantly associated with baseline prevalence and severity of AD, but not with incidence of AD. (eur.nl)
  • Conclusions Gelsolin, Clusterin and CD5L are potential plasma biomarkers to differentiate the healthy controls, ALS patients with and without CI. (bmj.com)
  • Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment. (ox.ac.uk)
  • Our main aim was to examine associations between plasma clusterin concentration and longitudinal changes in brain volume in normal aging and mild cognitive impairment (MCI). (ox.ac.uk)
  • Clusterin concentration was assayed by ELISA in plasma samples collected within a year of the baseline MRI. (ox.ac.uk)
  • Mixed effects regression models investigated whether plasma clusterin concentration was associated with rates of brain atrophy for control and MCI groups and whether these associations differed between groups. (ox.ac.uk)
  • In a separate autopsy sample of individuals with AD (N=17) and healthy controls (N=4), we examined the association between antemortem clusterin concentration in plasma and postmortem levels in the superior temporal gyrus, hippocampus and cerebellum. (ox.ac.uk)
  • The associations of plasma clusterin concentration with rates of change in brain volume were significantly different between MCI and control groups in several volumes including whole brain, ventricular CSF, temporal gray matter as well as parahippocampal, superior temporal and cingulate gyri. (ox.ac.uk)
  • Within the MCI but not control group, higher baseline concentration of plasma clusterin was associated with slower rates of brain atrophy in these regions. (ox.ac.uk)
  • In the combined autopsy sample of AD and control cases, representing a range of severity in AD pathology, we observed a significant association between clusterin concentration in the plasma and that in the superior temporal gyrus. (ox.ac.uk)
  • Plasma clusterin is one such biomarker showing promise as levels differ between healthy individuals and those with mild cognitive impairment (MCI) and AD. (edu.au)
  • An increased percentage methylation at CpG_16 was associated with elevated plasma clusterin (⍴=0.1858, p=0.0034, q=0.0157) within the HC group, which remained as a trend in the HC Aβ+ after FDR correction (β=0.2704, p=0.0043, q=0.0817). (edu.au)
  • The investigations presented in this thesis have explored the involvement of clusterin (CLU), a plasma protein, in transthyretin (TTR) and immunoglobulin light chain (LC) forms of systemic amyloidosis. (bu.edu)
  • Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease. (ox.ac.uk)
  • Increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-beta burden in the medial temporal lobe. (ox.ac.uk)
  • APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques. (ox.ac.uk)
  • Cyclic fluctuations of plasma clusterin were preserved under fasting and unexpected meal condition, suggesting that rhythmic oscillations in plasma clusterin levels are not generated by meal -related cues . (bvsalud.org)
  • These findings firstly demonstrate a novel pattern of plasma clusterin fluctuations with extremely regular cycles. (bvsalud.org)
  • The immunohistochemical distribution of clusterin (SP40,40, SGP-2) was determined in Alzheimer disease (AD) and normal human brain tissue and compared with the distributions of vitronectin, protectin and the complement membrane attack complex (MAC). (nih.gov)
  • Human native Clusterin was filtered (0.4µm) and lyophilized from 0.5mg/ml in 0.1M phosphate buffer, 0.15M NaCl pH 7.5. (prospecbio.com)
  • Circulating human clusterin exhibited similar associations. (diabetesjournals.org)
  • We also showed that in Drosophila photoreceptor cells, clusterin co-expression gave ER stress-dependent protection against proteotoxicity arising from both Huntingtin-Q128 and mutant (R406W) human tau. (edu.au)
  • Interestingly, clusterin associates with altered elastic fibers in human photoaged skin and prevents UV-induced elastin aggregation in vitro. (ovid.com)
  • In the current communication, we provide data that confirms the expression of clusterin in a number of different human eye tissues and establishes the expression profile of this gene in monkey derived eye tissues. (edu.au)
  • The issue that we sought to examine is whether a broad profile of clusterin expression in the eye is consistent in primates (monkey and human). (edu.au)
  • Clusterin is expressed in a broad range of eye tissues in both human and monkey, suggesting that this is a characteristic feature in primates. (edu.au)
  • Roles of clusterin in progression, chemoresistance and metastasis of human ovarian cancer. (semanticscholar.org)
  • Hepatitis delta virus epigenetically enhances clusterin expression via histone acetylation in human hepatocellular carcinoma cells. (semanticscholar.org)
  • Clusterin is overexpressed in human prostate cancer, breast cancers and squamous cell carcinomas. (bio-rad-antibodies.com)
  • You need info about Human Clusterin (CLU) ELISA Kit or any other Gentaur produtct? (gentaurshop.com)
  • We examined the relationship between clusterin and activated complement in human heart infarction and evaluated the effect of this protein on ischemic rat neonatal cardiomyoblasts (H9c2) and isolated adult ventricular rat cardiomyocytes as in vitro models of acute myocardial infarction. (vumc.nl)
  • Clusterin protects cells by inhibiting complement and colocalizes with complement on jeopardized human cardiomyocytes after infarction. (vumc.nl)
  • The distribution of clusterin and complement factor C3d was evaluated in the infarcted human heart. (vumc.nl)
  • The binding of endogenous and purified human clusterin on H9c2 cells was analyzed by flow cytometry. (vumc.nl)
  • In human myocardial infarcts, clusterin was found on scattered, morphologically viable cardiomyocytes within the infarcted area that were negative for complement. (vumc.nl)
  • To test this hypothesis, a single cell suspension of LLC-PK 1 cells (porcine proximal tubular cell line) treated with albumin (control) was compared to cells aggregated with fibrinogen or purified human clusterin (aggregation graded 0 to 4). (elsevier.com)
  • The primary objective of this clinical study was to determine a biologically effective dose of OGX-011 that would inhibit clusterin expression in human cancer. (oup.com)
  • Clusterin associated protein 1, also known as CLUAP1, is a human gene. (wikipedia.org)
  • A Role for Clusterin in Exfoliation Syndrome and Exfoliation Glaucoma? (ovid.com)
  • Although CLU has been considered as a therapeutic target in AD, cancer and dry eye, a role for clusterin in XFS/XFG needs to be better defined before therapeutic approaches involving CLU can be entertained. (ovid.com)
  • A direct role for clusterin in programmed cell death in the rat CNS was subsequently disclosed in a study by Garden and coworkers32 using in situ hybridization. (mussenhealth.us)
  • Consistent with these data and supportive of a role for clusterin in the maturation of the nervous tissue are the observations made by O'Bryan et al33 during neuronal development in the mouse. (mussenhealth.us)
  • Furthermore, the effect of clusterin on the viability of ischemically challenged H9c2 cells and isolated adult ventricular rat cardiomyocytes was analyzed. (vumc.nl)
  • In addition, the protective effect of clusterin is independednt on its receptor megalin, because inhibition of megalin has no effect on clusturin-mediated Akt/GSK-3β phosphoylation and H9c2 cell viability. (elsevier.com)
  • In situ hybridization was used to precisely localize clusterin transcripts in articular cartilage, where it was found that clusterin expression was confined to the articular surface in both immature and mature samples. (cf.ac.uk)
  • These results imply that clusterin is a secretory molecule having endocrine and/or paracrine actions in parallel with glucagon. (bioscientifica.com)
  • A genuine function of clusterin has not been defined. (prospecbio.com)
  • However, the physiological function of clusterin in the central nervous system remains largely unknown. (biomedcentral.com)
  • Involvement of clusterin and the aggresome in abnormal protein deposits in myofibrillar myopathies and inclusion body myositis. (semanticscholar.org)
  • Distribution of clusterin in Alzheimer brain tissue. (nih.gov)
  • A secondary objective was to examine associations between peripheral concentration of clusterin and its concentration in the brain within regions that undergo neuropathological changes in AD. (ox.ac.uk)
  • Furthermore, peripheral concentration of clusterin also appears to reflect its concentration within brain regions vulnerable to AD pathology. (ox.ac.uk)
  • Resistant cells were characterised by higher levels of cytoplasmic clusterin than sensitive cells, and antiestrogen treatments up-regulated clusterin levels in both sensitive and resistant cell lines. (spandidos-publications.com)
  • We therefore concluded that: i) basal clusterin levels are higher in antiestrogen resistant cells, ii) clusterin is up-regulated following antiestrogen treatment independently of the sensitivity of the cell line, iii) down-regulation of cytoplasmic clusterin restores sensitivity to toremifene in the antiestrogen-resistant cell line. (spandidos-publications.com)
  • Likewise, none of the PCNA or vimentin-positive cells expressed clusterin at detectable levels. (jci.org)
  • In this study the association of the AD clusterin common risk polymorphism rs9331888 with blood clusterin levels was tested in 104 AD subjects and 104 healthy controls. (cdc.gov)
  • This study indicates that the rs9331888 AD-risk variant is associated with low blood clusterin levels. (cdc.gov)
  • Experimental and clinical studies have associated elevated clusterin (CLU) levels with development of treatment resistance in prostate, lung, breast, ovarian, and other cancers ( 7-12 ). (aacrjournals.org)
  • During the light -on period, circulating clusterin levels showed fluctuating curves with 4 hours regular intervals with sharp peaks and troughs. (bvsalud.org)