• Sterol regulatory element-binding protein 2 (SREBP-2) also known as sterol regulatory element binding transcription factor 2 (SREBF2) is a protein that in humans is encoded by the SREBF2 gene. (wikipedia.org)
  • We formulate a deterministic nonlinear ordinary differential equation model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in an hepatocyte. (reading.ac.uk)
  • The mathematical model includes a description of genetic transcription by SREBP-2 which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a main precursor of cholesterol synthesis. (reading.ac.uk)
  • Cholesterol synthesis subsequently leads to the regulation of SREBP-2 via a negative feedback formulation. (reading.ac.uk)
  • Parameterised with data from the literature, the model is used to understand how SREBP-2 transcription and regulation affects cellular cholesterol concentration. (reading.ac.uk)
  • Western blot analysis of SREBP-2. (bdbiosciences.com)
  • Cell lysates were probed with Purified Mouse Anti-SREBP-2 (Cat. (bdbiosciences.com)
  • As apoptosis is induced, the SREBP-2 125 kDa precursor is cleaved to its ~70 kDa size. (bdbiosciences.com)
  • Human SREBP-2 aa. (bdbiosciences.com)
  • SREBP-1 and -2 (sterol-regulatory element binding proteins-1 and -2) are transcription factors which participate in the control of cholesterol homeostasis. (bdbiosciences.com)
  • SREBP proteins, which are attached to the endoplasmic reticulum and nuclear envelope, are proteolytically cleaved and thus activated in response to conditions of low cellular sterol. (bdbiosciences.com)
  • Upon activation of SREBP-1 or -2, a ~480-500 amino acid, N-terminal cleavage fragment of these proteins enters the nucleus and activates transcription of enzymes and other proteins required for cholesterol synthesis. (bdbiosciences.com)
  • SREBP proteins containing point mutations at caspase-3 cleavage sites (Asp460 in SREBP-1 and Asp468 in SREBP-2) do not become cleaved following induction of apoptosis, suggesting that SREBPs may play some role in apoptotic processes. (bdbiosciences.com)
  • However, sterol-regulated vs. apoptosis-associated cleavage of SREBP proteins appears to be independently regulated. (bdbiosciences.com)
  • On SDS-PAGE, sterol-regulated cleavage fragments of SREBP proteins migrate more slowly (i.e., higher molecular weight) than do staurosporin-induced fragments. (bdbiosciences.com)
  • Essential FA, mainly polyunsaturated fatty acids (PUFA), may modulate gene expression in diverse biological processes thought regulating transcription factors (TF), including peroxisome proliferator receptors (PPAR) , liver X receptors (LXR) , and sterol regulatory element-binding proteins ( SREBP ) 3 . (nature.com)
  • Sterol regulatory element binding protein (SREBP)-1 is a transcription factor with important roles in the control of fatty acid metabolism and adipogenesis. (diabetesjournals.org)
  • Out of the three isoforms present (SREBP-1a, SREBP-1c and SREBP-2), SREBP-2 has been implicated more directly in the synthesis of cholesterol during metabolism. (novusbio.com)
  • Similar to SREBP-1a and SREBP-1c, SREBP-2 acts by first binding to sterol regulatory DNA sequences, and subsequently up-regulating the synthesis of enzymes involved in sterol biosynthesis. (novusbio.com)
  • SREBP-2 is expressed in both the cytoplasm and nucleus on a subcellular level, depending on the state of the protein. (novusbio.com)
  • This interaction prevents the cleavage of SREBP-2, which results in the synthesis of cholesterol and uptake of LDL despite high levels of present sterols. (novusbio.com)
  • Transfection of HepG2 cells with sense or antisense miR-370 or miR-122 upregulated and downregulated, respectively, the transcription factor sterol-regulatory element binding protein 1c (SREBP-1c) and the enzymes diacylglycerol acyltransferase-2 (DGAT2), fatty acid synthase (FAS), and acyl-CoA carboxylase 1 (ACC1) that regulate fatty acid and triglyceride biosynthesis. (nih.gov)
  • Mechanistically, FSH, via binding to hepatic FSHRs, activates the Gi2α/β-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter, thus preventing FoxO1 from repressing SREBP-2 gene transcription. (nature.com)
  • This effect, in turn, results in the upregulation of SREBP-2 , which drives HMGCR nascent transcription and de novo cholesterol biosynthesis, leading to the increase of cholesterol accumulation. (nature.com)
  • Expression of sterol regulatory element binding protein 1 (SREBP-1), ATP-citrate lyase (ACL), fatty acid synthase (FAS), malic enzyme (ME), acetyl-CoA carboxylase (ACC), and stearoyl-CoA (?9) desaturase 1 (SCD1) genes in ad lib birds declined from their highest levels just prior to photo-stimulation to reduced levels as the birds came into and maintained egg production. (usda.gov)
  • Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. (thebiogrid.org)
  • In this model of stress-induced cell senescence using DFO and H 2 O 2 , the phosphorylation profile of glycogen synthase kinase 3α (GSK3α) and β corresponded closely to the expression profile of the mature form of SREBP-1 protein. (koreamed.org)
  • By contrast, addition of free fatty acids (FFA, oleic acid/palmitic acid 2:1) caused aggravation of LPS-induced inflammatory reaction and an increase of Srebp-1c relative to PPARα. (frontiersin.org)
  • 2007). Suppression of the genes, which are involved in lipogenesis (ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA-desaturase 1 or sterol regulatory element-binding protein 1(SREBP-1)), reduced proliferation and survival of hepatic carcinoma cells (Calvisi et al. (webmedcentral.com)
  • Using RNA sequencing and gene set enrichment analysis (GSEA), Set7 inhibitors upregulated the expression of genes involved in the control of cholesterol Sterol Regulatory Element-Binding Proteins (SREBP), cholesterol and fatty acyl biosynthesis. (edu.au)
  • Sterol regulatory element-binding proteins (SREBPs) compose a family of transcriptional factors that regulate the expression of various genes required for the synthesis of phospholipids, fatty acids, and cholesterol. (novusbio.com)
  • Brown, MS & Goldstein, JL 1998, ' Seventeenth Marabou Symposium on Diet and Genetic Interactions: Sterol regulatory element binding proteins (SREBPs): Controllers of lipid synthesis and cellular uptake ', Nutrition Reviews , vol. 56, no. 2 II, pp. (elsevierpure.com)
  • Exposure of isolated human adipocytes to tumor necrosis factor-α (TNF-α) produced a marked and specific decrease in the mRNA encoding the SREBP1c isoform and completely blocked the insulin-induced cleavage of SREBP1 protein. (diabetesjournals.org)
  • Upon binding to its receptor, insulin activates a cascade of intracellular signaling events. (alliedacademies.org)
  • Insulin signaling pathway activates phosphatidylinositol 3-kinase (PI3K), which phosphorylates and activates Akt (also known as protein kinase B). Akt regulates glucose transport by promoting the translocation of glucose transporters, such as GLUT4, to the plasma membrane. (alliedacademies.org)
  • In the poster section, Joanna Shisler (University of Illinois at Urbana-Champaign [UIUC], Urbana) reported that the modified virus, Ankara, activates nuclear factor κB through the mitogen-activated protein kinase, extracellular signal–regulated kinase (MEK)/extracellular signal–regulated kinase (ERK) pathway, possibly facilitating the host immune response. (cdc.gov)
  • Methionine is an essential amino acid, that affects the metabolism of protein, lipid and glucose. (researchsquare.com)
  • Cholesterol is a sterol, a type of lipid molecule composed of a complex structure of four fused hydrocarbon rings. (biochemden.com)
  • Because levels of transcription factor CCAAT/enhancer binding protein-β, peroxisome proliferator-activated receptor-γ, and lipoprotein lipase are also increased, lipid transport into cells and fatty acid synthesis within cells is increased ( 8 - 15 ). (cdc.gov)
  • This gene encodes a ubiquitously expressed transcription factor that controls cholesterol homeostasis by stimulating transcription of sterol-regulated genes. (wikipedia.org)
  • Hepatic expression of fatty acid binding protein (FABP), very low density apolipoprotein II (ApoVLDL-II) and apolipoprotein B (ApoB) genes increased in both ad lib and restricted breeders following photo-stimulation, whereas apolipoprotein A1 (ApoA1) gene expression declined in both groups. (usda.gov)
  • Transcriptome profiling by RNA sequencing and GSEA studies showed PFI-2 and cyproheptadine hydrochloride can attenuate TNF-α induced gene expression. (edu.au)
  • Having shown that pharmacological inhibition of Set7 activity attenuates TNF-α driven gene expression, we proposed that PFI-2 and cyproheptadine hydrochloride could suppress TNF-α induced cytokine release. (edu.au)
  • The discovery of the NPC1 gene by Carstea et al[1] in 1997 has stimulated much research in Niemann-Pick disease, the NPC1 gene product, sterol trafficking, and gene therapy in animal models. (medscape.com)
  • Hence, evidenced the blocking of phosphatidylinositol 3-kinase/protein kinase B signaling pathway. (ijpsonline.com)
  • It induced apoptosis, suppressed cell migration and invasion, blocked cell cycle and phosphatidylinositol 3-kinase/ protein kinase B signaling pathway. (ijpsonline.com)
  • High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. (biomedcentral.com)
  • BCL2 proteins are described as 'crucial regulators of apoptosis' (PMID:15868100)and the intrinsic apoptosis pathway is initiated by the release of mitochondrial cytochrome c into the cytoplasm, which results in the activation of caspases (15102863) - help in generating a defintion for intrinsic apoptosis? (geneontology.org)
  • In adipocytes, the sterol regulatory element binding protein pathway is increased, resulting in increases in levels of sterol regulatory element binding protein 1 and fatty acid synthase. (cdc.gov)
  • Therefore, it is important to understand the genetic regulatory mechanisms for controlling fat metabolism in poultry during rearing and breeding periods of production. (usda.gov)
  • We also demonstrate that HLCs express proteins essential for lipoprotein metabolism, secrete authentic VLDL particles, and respond to metabolic perturbations, supporting their value for modeling hepatosteatosis and VLDL metabolism in vitro. (columbia.edu)
  • Conclusion: In the present study, RBSO appeared to improve sugar metabolism as evidenced by reduction in FBS, PPBS and HbA1c in type-2 diabetic patients. (longdom.org)
  • These data suggest that Treg control of Teff metabolism regulates inflammation differentially in prediabetes compared with type 2 diabetes. (diabetesjournals.org)
  • In response to the elevated glutamate in the liver, the expression of metabotropic glutamate receptor 5 (mGluR5) is up-regulated in hepatic stellate cells (HSCs) along with enhanced production of 2-arachidonoylglycerol, which in turn stimulates cannabinoid receptor 1 (CB 1 R) on neighboring hepatocytes to increase de novo lipogenesis. (e-cmh.org)
  • Interestingly, although the increased expression of CYP2E1-mediated xCT and ROS generation are mainly observed at the perivenous area (zone 3), fat accumulation is mostly detected at hepatic zone 2. (e-cmh.org)
  • In addition, muscular PEPCK and glycogen synthase, and hepatic glucose transporters 2 mRNA levels were induced by 1.28% methionine. (researchsquare.com)
  • A basic helix-loop-helix leucine zipper (bHLHZ) transcription factor and proto-oncogene protein that functions in cell growth and proliferation. (bvsalud.org)
  • Jurkat (ATCC TIB-152) cells were left untreated (lanes 1 & 2) or treated with 1 µM Staurosporin for 4 hours (lanes 3 & 4) to induce apoptosis. (bdbiosciences.com)
  • This revealed increased expression of B-cell lymphoma 2 associated X and reduced expression of B-cell lymphoma 2, indicating apoptosis induction by piperine. (ijpsonline.com)
  • does all activation of caspases require other proteins also involved in apoptosis - therefore shouldn't this term be a part of apoptosis? (geneontology.org)
  • how to decide whether a protein is involved in '+ve reg of apoptosis or induction ([GO:0006917])?emily. (geneontology.org)
  • When cellular cholesterol levels are depleted, these genes are all transcribed in abundant amounts, and their transcription is repressed when sterols build up within the cell. (elsevierpure.com)
  • On the other hand, pharmacological inhibition of Set7 by PFI-2 and cyproheptadine hydrochloride reduced the expression of genes implicated in cell cycle and smooth muscle cell contraction. (edu.au)
  • Western blotting assay was implemented to check the levels of phosphatidylinositol 3-kinase and protein kinase B. Results revealed that piperine induced dose reliant cytotoxicity in MCF-7 human breast cancer cells. (ijpsonline.com)
  • Finally, Western blotting assay predicted constant expression of phosphatidylinositol 3-kinase and protein kinase B and reduced expression of phosphorylated phosphatidylinositol 3-kinase. (ijpsonline.com)
  • The protein levels of phospho-phosphatidylinositol 3-kinase, protein kinase B, phospho-eukaryotic initiation factor 4E binding protein-1 (p-4E-BP1), 4E-BP1 and ribosomal protein S6 kinase 1, in the liver of fish fed the 0.84% diet were higher than those in fish fed the 0.40% diet. (researchsquare.com)
  • AMP-Activated Protein Kinase (AMPK) is a master regulator of cellular energy status. (alliedacademies.org)
  • We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 µM) of deferoxamine (DFO) and H 2 O 2 . (koreamed.org)
  • A disparate array of plasma/serum markers provides evidence for chronic inflammation in prediabetes ( 2 , 3 ) that contrasts with our rich understanding of cellular sources of inflammation in human type 2 diabetes and animal models of insulin resistance (IR) ( 4 ). (diabetesjournals.org)
  • The sympathetic nervous system regulates this function through β-adrenergic stimulation of brown mature adipocytes' dissipation of energy in the form of heat mediated by mitochondrial uncoupling protein-1 (UCP-1) activation. (springer.com)
  • Obesity and its metabolic complications (e.g. type 2 diabetes, cardiometabolic disorders) contributing to the metabolic syndrome represent one of the most important public health problems, with societal and economic implications urging for new therapeutic strategies and effective social policies. (springer.com)
  • Type 2 Diabetes is associated with chronic hyperglycemia due to metabolic disorders caused by insulin resistance [ 1 ]. (longdom.org)
  • Obesity-associated prediabetes is a compromised metabolic state defined mainly by hyperglycemia that falls short of criteria for type 2 diabetes and is less likely to perpetuate complications like renal and cardiovascular diseases. (diabetesjournals.org)
  • RNA-sequencing and qPCR validation reveal that the Sterol Regulatory Element Binding Protein 2 (SREBP2)-mediated transcriptional program regulating cholesterol synthesis is significantly increased in TM6SF2 KO iPSCs. (columbia.edu)
  • Inhibition of triacylglycerol (TAG) synthesis via diacylglycerol acyltransferase 2 (DGAT2) antisense oligonucleotides improves liver steatosis (Yamaguchi et al. (webmedcentral.com)
  • Cholesterol synthesis is a complex process involving a series of enzymatic reactions and regulatory steps in various cell organelles. (biochemden.com)
  • When activated, AMPK phosphorylates and inhibits enzymes involved in ATP-consuming processes, such as fatty acid synthesis (e.g., acetyl-CoA carboxylase, ACC) and protein synthesis (e.g., mammalian target of rapamycin, mTOR). (alliedacademies.org)
  • The Niemann-Pick group of diseases can be subclassified into two categories: (1) those with a primary deficiency in acid sphingomyelinase (ASM) activity (ie, types A and B) and (2) those with defective intracellular processing and transporting of low-density lipoprotein (LDL)-derived cholesterol (ie, type C). (medscape.com)
  • The formation of a complex then enables Lon to degrade free ribosomal proteins. (go.jp)
  • Certain very abundant ribosomal proteins can be the sacrificial substrates targeted for degradation at the onset of the downshift. (go.jp)
  • It has been known to interact and form a complex with the SCAP protein at the ER, in turn inhibiting interaction between SCAP and SEC24B. (novusbio.com)
  • The IgG-1C6 antibody may be used for western blot analysis (2 µg/ml) and immunoprecipitation (2 µg antibody/300-500 µg of total protein lysate). (bdbiosciences.com)
  • Western Blot: SREBP2 Antibody (1D2) [NBP1-54446] - Lane1: HEp-2 cells. (novusbio.com)
  • Its oils are rich sources of unsaturated fatty acids, such as monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids, which are previously associated with the prevention of health disorders because of their anti-inflammatory effects and cell membrane properties and structure 2 . (nature.com)
  • Of note, circulating free fatty acids may also function as endogenous ligands for TLR binding as so-called danger associated molecular patterns, DAMPs. (frontiersin.org)
  • U-937 human histiocytic lymphoma cells (ATCC CRL-1593) or HeLa human cervical carcinoma cells (ATCC CCL-2) are recommended as additional positive controls. (bdbiosciences.com)
  • Sodium azide may be removed by washing stained cells or plate-bound antibody or dialyzing soluble antibody in sodium azide-free buffer. (bdbiosciences.com)
  • Lane 2: MCF-7 cells. (novusbio.com)
  • To solve this dilemma, cells must use their own proteins as sources of amino acids in response to the nutritional downshift. (go.jp)
  • BC comprises of variant subtypes and those subtypes arise from basal progenitor or luminal progenitor cells undergoing different genetic mutations[ 2 ]. (ijpsonline.com)
  • In addition to loss of replicative capacity, senescent cells display alterations in morphology, mass, and the dynamics of subcellular organelles [ 2 - 4 ]. (koreamed.org)
  • In parallel, TRPA1 activation also plays regulatory roles by affecting the survival of NK cells to limit uncontrolled and prolonged NK cell-mediated cytotoxicity. (bvsalud.org)
  • Our results indicate that the activation of TRPA1 is an important regulatory signal for NK cells, and agonists of TRPA1 could be used to strengthen the tumor response of the immune system. (bvsalud.org)
  • Overexpression of TRPA1 in A549 cells increased acrolein sensitivity and the level of protein-conjugated acrolein (PC-Acro), while knockdown of TRPA1 in A549 cells or treatment with a TRPA1 antagonist caused tolerance to acrolein. (bvsalud.org)
  • Regulatory T cells (Treg) control mitochondrial function and cytokine production by CD4 + effector T cells (Teff) in prediabetes and type 2 diabetes by supporting T helper (Th)17 or Th1 cytokine production, respectively. (diabetesjournals.org)
  • Set7 is also associated with regulation of different non-histone proteins including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). (edu.au)
  • In this project, HMEC-1 cells were used to assess the Set7 inhibitors, PFI-2 and cyproheptadine hydrochloride mediated regulation under basal conditions and during TNF-α induced inflammation. (edu.au)
  • The World Health Organization reported that A significant number of patients with type 2 diabetes die from cardiovascular diseases [ 3 ]. (longdom.org)
  • Chronic alcohol intake leads to a broad spectrum of alcoholic liver disease (ALD) such as simple steatosis, steatohepatitis, hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma [ 2 , 4 ]. (e-cmh.org)
  • Diabetes Metab J. 2023;47(2):153-163. (e-dmj.org)
  • Samples of liver and abdominal fat pad were collected at the following times: 1) just prior to photo-stimulation, 2) after photo-stimulation at first egg, and 3) through peak egg production. (usda.gov)
  • Given the pivotal role that lipoproteins play at the juncture of these two conditions, researchers hypothesize that the ER-membrane spanning TM6SF2 protein regulates the degree of lipidation of VLDL particles synthesized in the liver. (columbia.edu)
  • The increase in the incidence of type 2 diabetes is largely attributable to lifestyle changes including diet, increasing age and sedentary life [ 2 ]. (longdom.org)
  • Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two growing and related diseases in general population and particularly in elderly people. (hindawi.com)
  • However, in the context of sustained obesity, WAT undergoes fibro-inflammation, which compromises its functionality, contributing to increased risk of type 2 diabetes and cardiovascular diseases. (springer.com)
  • PMID:14996496, table 1 provides links to papers that describe subcellular location of many pro- and anti-apoptotic proteins. (geneontology.org)
  • Transcript levels of SREBP1c, the most abundant isoform in adipose tissue, were significantly decreased in the subcutaneous adipose tissue of obese normoglycemic and type 2 diabetic subjects compared with that of nonobese normoglycemic control subjects. (diabetesjournals.org)
  • Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. (biomedcentral.com)
  • Cytochrome c then forms a multi-protein complex known as the 'apoptosome' and initiates activation of the caspase cascade through caspase 9. (geneontology.org)
  • Simultaneously detect the levels of these cytokines, chemokines, and acute phase proteins in a single sample. (rndsystems.com)
  • Smoking enhances the expression of angiotensin-converting enzyme 2 involved in the efficiency of severe acute respiratory syndrome coronavirus 2 infection. (shimamlab.info)
  • Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two related and growing health care problems [ 1 , 2 ], with an increasing trend in elderly people [ 3 ]. (hindawi.com)
  • In skeletal muscle, SREBP1 expression was significantly reduced in type 2 diabetic subjects but not in obese subjects. (diabetesjournals.org)
  • The specific reduction in the SREBP1c isoform seen in the adipose tissue of obese and type 2 diabetic subjects can be recapitulated ex vivo by TNF-α, suggesting a possible mechanism for this association. (diabetesjournals.org)
  • These remain largely nonactionable and contrast with our rich understanding of inflammation in human type 2 diabetes. (diabetesjournals.org)
  • The very large pool of people with prediabetes are at high risk for type 2 diabetes, although prediabetes is very reversible through lifestyle changes, while medications like metformin delay progression to type 2 diabetes ( 1 ). (diabetesjournals.org)
  • A better understanding of prediabetes is an important goal that could prevent a considerable number of type 2 diabetes cases. (diabetesjournals.org)
  • Mechanistically, QL-007 blocked the encapsidation of pgRNA and induced aberrant polymers assembly at concentrations ≥100 nM, while having no impact on the stability of core proteins. (bvsalud.org)