• Attenuation of inducible nitric oxide synthase gene expression by delta 9-tetrahydrocannabinol is mediated through the inhibition of nuclear factor- kappa B/Rel activation. (aspetjournals.org)
  • In the current study, we show that delta 9-THC produces a marked inhibition of inducible nitric oxide synthase (iNOS) transcription and nitric oxide production by the macrophage line RAW 264.7 in response to lipopolysaccharide (LPS). (aspetjournals.org)
  • M1 macrophages are associated with the expression of interleukin (IL)-1, -12, TNF-α and inducible nitric oxide synthase (iNOS) 7 . (ersjournals.com)
  • The expression and activity of inducible nitric oxide synthase, an intracellular marker of M1, were increased by MWCNTs. (cdc.gov)
  • Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice. (bvsalud.org)
  • The HIF-1 protein is composed of two HIF-1α and HIF-1β/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. (biomedcentral.com)
  • HLE-B3 cells, maintained in a continuous hypoxic environment (1% oxygen), were treated with SB216763, a specific inhibitor of glycogen synthase kinase-3β (GSK-3β) catalytic activity. (molvis.org)
  • Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. (ox.ac.uk)
  • The most important of these, although not capable of driving hypoxic induction in isolation, had the consensus of a hypoxia-inducible factor 1 (HIF-1) site, and cross-competed for the binding of HIF-1 with functionally active Epo and phosphoglycerate kinase-1 sequences. (ox.ac.uk)
  • The second domain was positioned close to the HIF-1 site, in an analogous position to one of the critical regions in the Epo 3' hypoxic enhancer. (ox.ac.uk)
  • In addition to hypoxic conditions, non-hypoxic stimuli such as growth factors also activate expression of HIF-1. (korea.ac.kr)
  • however, hypoxic conditions markedly increased the abundance of HIF-1α protein, especially in nuclei of pTr cells. (korea.ac.kr)
  • Among these transcription factors, hypoxia-inducible factor-1 (HIF-1) is one of the most important factors that play a critical role in controlling oxygen delivery and metabolic adaptation to hypoxic conditions. (spandidos-publications.com)
  • Exposure to a variety of growth factors has also been shown to increase HIF-1 activity in normoxic and hypoxic conditions. (spandidos-publications.com)
  • To test this, we pre-exposed immortalized N9 and primary microglia to hypoxia (1% O 2 ) for 16 h and then challenged them with pro-inflammatory lipopolysaccharide (LPS) either immediately or 3-6 days following hypoxic exposure. (frontiersin.org)
  • At decreased oxygen tensions, hypoxia-inducible factors (HIFs) 1 and 2 are stabilized and mediate a hypoxic response, primarily by acting as transcription factors. (lu.se)
  • Retinal neuroprotection by hypoxic preconditioning is independent of hypoxia-inducible factor-1α expression in photoreceptors. (hslu.ch)
  • A hypoxia-inducible factor-1α (HIF-1α) translation inhibitor and an HIF-2α translation inhibitor were independently employed to evaluate the effect of hypoxia inducible factor inhibition on EMT marker protein and VEGF expression. (molvis.org)
  • Hypoxia-inducible factor prolyl hydroxylase inhibition: Robust new target or another big bust for stroke therapeutics? (wikipedia.org)
  • Hypoxia maintains HIFα protein expression through inhibition of prolyl hydroxylases and IL-1 is suggested to effect subunit expression at the level of transcription and in a similarly post-translational fashion [ 26 ]. (biomedcentral.com)
  • This EGF-mediated increase in HIF-1α protein was blocked through inhibition of translation by cycloheximide. (korea.ac.kr)
  • Chlamydial inhibition of MHC class II expression is correlated with degradation of upstream stimulatory factor (USF)-1, a constitutively and ubiquitously expressed transcription factor required for IFN-γ induction of class II transactivator (CIITA) but not of IRF-1 and ICAM-1. (silverchair.com)
  • In occurs through the inhibition of DNA binding of cognate cis- hematopoiesis there exist several lineage branch points with regulatory motif while in the other case DNA binding is unaffected identified key transcription factors and external signals [3-5]. (lu.se)
  • Ngb is a neuronal hemeprotein that shares its capability for oxygen binding while Hif-1α is a transcription factor that responds to decreases in available oxygen in the cellular environment or hypoxia. (scielo.br)
  • Hypoxia-inducible factor (HIF) is an evolutionarily conserved transcription factor that allows the cell to respond physiologically to low concentrations of oxygen. (wikipedia.org)
  • These subunits are members of the basic helix-loop-helix (bHLH) transcription factor superfamily containing a PAS [PER (Period Clock) -ARNT-SIM (Single-minded)] domain [ 2 ]. (biomedcentral.com)
  • The study results indicated that cytotrophoblasts respond to an ischemic environment by their nuclear expression of HIF-1α, and thus we conclude that this transcription factor has a significant potential as a marker for preeclampsia. (edu.au)
  • The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. (scielo.br)
  • The Ngb and Hif-1α expression showed similarities and differences. (scielo.br)
  • The purpose of this study was to identify potential therapeutic strategies to slow down or prevent the expression of early-onset epithelial to mesenchymal transition (EMT) marker proteins (fibronectin and alpha smooth muscle actin, α-SMA) without sacrificing the synthesis and accumulation of the prosurvival protein vascular endothelial growth factor (VEGF) in cultured virally transformed human lens epithelial (HLE) cells. (molvis.org)
  • In conjunction with SB216763, coadministration of an HIF-1α translation inhibitor, but not an HIF-2α translation inhibitor, markedly suppressed the expression of fibronectin and α-SMA without affecting VEGF levels. (molvis.org)
  • Instead, the loss of HIF-1α (but not HIF-2α) decreases the expression of the EMT marker proteins without sacrificing the levels of the prosurvival protein VEGF. (molvis.org)
  • and the constitutive transcription factors (CTFs) CREB, CREM, ATF-2 and SRF as they pertain to gene expression in the mammalian nervous system. (nih.gov)
  • In the first part we consider basic facts about the expression and activity of these transcription factors: the organization of the encoding genes and their promoters, the second messenger cascades converging on their regulatory promoter sites, the control of their transcription, the binding to dimeric partners and to specific DNA sequences, their trans-activation potential, and their posttranslational modifications. (nih.gov)
  • To understand the organization of cis-acting sequences that are responsible for oxygen-regulated gene expression, we have studied the 5' flanking region of the mouse gene encoding the hypoxically inducible enzyme lactate dehydrogenase A (LDH). (ox.ac.uk)
  • The impact of HIF-1α alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known. (biomedcentral.com)
  • Our results show for the first time that mRNA expression of a HIF-1α TAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis. (biomedcentral.com)
  • In this study, the mechanisms underlying low oxygen-dependent and epidermal growth factor (EGF)-dependent expression of HIF-1α were explored using porcine trophectoderm (pTr) cells. (korea.ac.kr)
  • Immunohistochemical studies for evaluating the expression of HIF-1α by these tissues were then performed. (edu.au)
  • We report that chlamydiae, which are obligate intracellular bacterial pathogens, can inhibit interferon (IFN)-γ-inducible major histocompatibility complex (MHC) class II expression. (silverchair.com)
  • However, the IFN-γ-induced IFN regulatory factor-1 (IRF-1) and intercellular adhesion molecule 1 (ICAM-1) expression is not affected, suggesting that chlamydia may selectively target the IFN-γ signaling pathways required for MHC class II expression. (silverchair.com)
  • CIITA is an obligate mediator of IFN-γ-inducible MHC class II expression. (silverchair.com)
  • Thus, diminished CIITA expression as a result of USF-1 degradation may account for the suppression of the IFN-γ-inducible MHC class II in chlamydia-infected cells. (silverchair.com)
  • Tlymphocyte recognition of MHC-peptide complexes on target cells is essential for mounting an antigen-specific immune attack ( 1 ), which may in turn select pathogens able to evade immune recognition by suppressing MHC expression on the infected cells ( 2 ). (silverchair.com)
  • To escape CD4 + T cell recognition, pathogens may need to inhibit the IFN-γ-inducible MHC class II expression. (silverchair.com)
  • It has been demonstrated that IFN-γ- inducible MHC class II expression is inhibited in cells infected with various intracellular pathogens ( 13 - 18 ), which suggests that suppression of IFN-γ-inducible MHC class II may represent an immune evasion strategy used by intracellular pathogens. (silverchair.com)
  • This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (topo‑I). Furthermore, celastrol prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). (spandidos-publications.com)
  • Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)
  • Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)
  • In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. (spandidos-publications.com)
  • An analysis of an interactome for apoptosis factor, Ei24/PIG8, using the inducible expression system and shotgun proteomics. (nih.gov)
  • The device was used to study the effect of different IH frequencies on HIF-1 expression. (ibecbarcelona.eu)
  • revised quantiles: high/low), IFN-1 mRNA expression (high/low) and BLyS protein level (high/low). (biomedcentral.com)
  • Treatment of murine macrophages (J774A.1) with Mitsui-7 MWCNTs increased the expression of Alox5 mRNA and protein in a concentration- and time-dependent manner. (cdc.gov)
  • ECM also modulates the bioavailability of many growth factors. (springer.com)
  • There are several factors (low temperature, hypoxia, strong ultraviolet light, and dryness) at high altitudes that affect the survival of mammals especially deoxygenated atmosphere which leads to inadequate oxygen reaching the animal's body. (scielo.br)
  • Hypoxia-inducible factor-proline dioxygenase (EC 1.14.11.29, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). (wikipedia.org)
  • Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. (biomedcentral.com)
  • In the middle section of HIF-1α lies a Pro-Ser-Thr oxygen-dependent degradation domain (ODDD, amino acids 401 to 603), which is responsible for the stability of the HIF-1α protein [ 12 ]. (biomedcentral.com)
  • Hypoxia-inducible factor (HIF)-1 is a master regulator whereby cells adapt to changes in oxygen concentrations. (korea.ac.kr)
  • The results of the present study suggest that pTr cells adapt to oxygen deficiency and proliferate in response to an oxygen-dependent HIF-1 system, and that EGF at maternal-conceptus interface can increase the abundance of HIF-1α protein via translational regulation through AKT, ERK1/2 and mTOR signaling cascades. (korea.ac.kr)
  • Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses to low oxygen and vital to many aspects of cancer biology. (spandidos-publications.com)
  • In hypoxia, several transcription factors are induced to respond to the decreased oxygen level. (spandidos-publications.com)
  • only HIF-1α is regulated by the oxygen tension ( 1 , 2 ). (spandidos-publications.com)
  • Furthermore, HIF-1α is also stabilized by reactive oxygen species (ROS), which block PHD activities ( 8 ). (spandidos-publications.com)
  • Hypoxia stabilises HIF-1α protein by relaxing its ubiquitin-proteasome degradation [ 12 ] and affects subcellular localisation, DNA binding capacity and transcriptional activation function of the HIF-1 complex. (biomedcentral.com)
  • The modified HIF-1α interacts with Von Hippel-Lindau (VHL), which is part of the E3 ubiquitin ligase complex targeting HIF-1α for 26S proteasomal degradation. (spandidos-publications.com)
  • Objective: The aim of this study was to analyze the possible influence of HIF-1α genetic polymorphisms on cancer susceptibility, tumor aggressiveness, and survival of patients with early-stage cervical cancer. (ewha.ac.kr)
  • Conclusions: Although HIF-1α genetic polymorphisms had little association with cervical cancer risk and prognosis, individual variance of HIF-1α gene may be associated with cervical cancer invasiveness. (ewha.ac.kr)
  • Polymorphisms in hypoxia inducible factor 1 and the initial clinical presentation of coronary disease. (stanford.edu)
  • The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. (bmj.com)
  • During hypoxia, an intricate balance exists between factors that induce or counteract apoptosis, or even stimulate proliferation. (bmj.com)
  • this association is primarily based on the HIF-1-mediated regulation of genes that play pivotal roles in the central features of cancer pathogenesis such as angiogenesis, invasion, metastasis and anti-apoptosis. (spandidos-publications.com)
  • Inactivation of VHL ubiquitin ligase is associated with normoxic stabilization of hypoxia-inducible factor-1α and 2-α (HIF-1α and HIF-2α), transcriptional regulators of tumor angiogenesis, invasion, survival, and glucose utilization. (aspetjournals.org)
  • Hypoxia is an important micro-environmental factor in promoting tumor progression. (spandidos-publications.com)
  • Consistent with M1 polarization, the MWCNTs induced the production and secretion of proinflammatory cytokines tumor necrosis factor-a and interleukin-1β, and proinflammatory LMs leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). (cdc.gov)
  • Even under normoxic conditions, the abundance of HIF-1α protein increased in response to EGF. (korea.ac.kr)
  • Under normoxic conditions, prolyl hydroxylases (PHDs) hydroxylate the cite-specific proline residues of HIF-1α in a reaction that uses O 2 as a substrate. (spandidos-publications.com)
  • HIF-1α is known to be mainly post-transcriptionally regulated by protein ubiquitination and interaction with the Von Hippel-Lindau tumour suppressor protein, and then degraded by the proteasome. (biomedcentral.com)
  • Currently, even in patients with stage IA disease, the 5-yr survival after putatively curative surgical resection is only 67% 1 . (ersjournals.com)
  • Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). (biomedcentral.com)
  • The quintessential pro-inflammatory cytokine Interleukin-1 (IL-1) canonically triggers a broad spectrum of physiological consequences. (biomedcentral.com)
  • The putative mechanism for cannabinoid biological action involves binding to cannabinoid receptor types 1 and 2 (CB1 and CB2) to negatively regulate adenylate cyclase and inhibit intracellular signaling via the cAMP cascade. (aspetjournals.org)
  • HIF-1α isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1α TAG ) and HIF-1α 736 mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues ( P = 0.009 and P = 0.004 respectively). (biomedcentral.com)
  • HIF-1α TAG mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status ( P = 0.005 and P = 0.033 respectively). (biomedcentral.com)
  • Alloswitch-1 is selective for the metabotropic glutamate receptor mGlu5 and enables the optical control of endogenous mGlu5 receptors. (ibecbarcelona.eu)
  • However, because the thrombopoietin receptor is the only growth factor receptor in hematopoietic stem cells, thrombocytosis can occur before erythrocytosis. (msdmanuals.com)
  • For example proteoglycans sequester biomolecules such as growth factors (TGF-β, VEGF, FGF etc.) and MMPs (Matrix Metalloproteinases). (springer.com)
  • Vascular endothelial growth factor (VEGF), a key component in the process of angiogenesis, is known to be produced by tumour-associated macrophages 17 , 18 , which have been traditionally reported as M2 macrophages. (ersjournals.com)
  • Activation of cAMP by forskolin had no effect on the level of LDH mRNA in normoxia, but produced a magnified response to hypoxia that was dependent upon the integrity of the CRE, indicating an interaction between inducible factors binding the HIF-1 and CRE sites. (ox.ac.uk)
  • LPS treatment of RAW 264.7 cells also induced the activation of the cAMP cascade, as indicated by an increase in binding of nuclear factors to the cAMP response element. (aspetjournals.org)
  • Loss of immune tolerance to autoantigens associated with a specific organ results in the activation of organ-specific T and B cells that in turn cause organ-specific inflammation and the development of autoimmune diseases such as multiple sclerosis (MS) ( 5 ), rheumatoid arthritis (RA) ( 6 ), psoriasis ( 7 ), and type 1 diabetes (T1D) ( 8 ). (frontiersin.org)
  • In a search for HIF-1 inhibitors, we identified celastrol as an inhibitor of HIF-1 activation from Tripterygium wilfordii. (spandidos-publications.com)
  • In the present study, we demonstrated the effect of celastrol on HIF-1 activation. (spandidos-publications.com)
  • Celastrol showed a potent inhibitory activity against HIF-1 activation induced by hypoxia in various human cancer cell lines. (spandidos-publications.com)
  • iNOS transcription, which is regulated in part by the nuclear factor-kappa B/Rel (NF-kappa B/Rel) family of transcription factors, has been shown to be under the control of the cAMP signaling cascade. (aspetjournals.org)
  • Inducible heat shock proteins (HSP) controlled by heat shock factor-1 (HSF-1) drive back renal cell injury style of ischemic renal injury (15-17). (sciencepop.org)
  • The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1α protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. (korea.ac.kr)
  • a protein component of a ubiquitin ligase complex) and hypoxia-inducible factors (a family of transcription factors activated by hypoxia). (lww.com)
  • In types of renal ischemia HSF-1 can be primarily triggered by metabolic tensions connected with ATP depletion (18 19 To comprehend better the part of HSP induction in ischemic renal damage we researched HSF-1 practical knockout mice (HSF-KO). (sciencepop.org)
  • Tonicity-responsive enhancer-binding protein (TonEBP), which is also known as nuclear factor of activated T cells 5 (NFAT5), was discovered 20 years ago as a transcriptional regulator of the cellular response to hypertonic (hyperosmotic salinity) stress in the renal medulla. (nature.com)
  • In humans, there are three isoforms of hypoxia-inducible factor-proline dioxygenase. (wikipedia.org)
  • This enzyme catalyses the following chemical reaction hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 ⇌ {\displaystyle \rightleftharpoons } hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 Hypoxia-inducible factor-proline dioxygenase contains iron, and requires ascorbate. (wikipedia.org)
  • The mammalian immune system evolved to protect our bodies from foreign pathogens and intrinsic aberrant malignancies while concurrently preventing deleterious immune responses toward self ( 1 ). (frontiersin.org)
  • In breast cancers HIF-1α splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival. (biomedcentral.com)
  • Background: Human papillomavirus can stabilize and induce hypoxia-inducible factor 1α (HIF-1α) protein, which is associated with diminished response to treatment and poor prognosis for cervical cancer. (ewha.ac.kr)
  • The M1 phenotype (classically activated) macrophages are thought to be induced by interferon-γ, with or without lipopolysaccharide and tumour necrosis factor (TNF)-α, and exert a cytotoxic effect against cancer cells. (ersjournals.com)
  • The prognostic relevance of HIF-1α protein overexpression has been shown in breast cancer. (biomedcentral.com)
  • International Journal of Gynecological Cancer , 21 (1), 2-7. (ewha.ac.kr)
  • However, since 2009 Associate Professor Currie's interests have expanded to include the contribution to tumour progression made by tumour infiltrating immune cell populations, breast cancer stem cell-like populations, and obesity-related factors. (otago.ac.nz)
  • Our data suggested that celastrol is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity. (spandidos-publications.com)
  • Diagnosis, treatment, prognostic factors and long-term outcome in papillary thyroid carcinoma. (medscape.com)
  • In addition, functional studies have shown that TonEBP is involved in the pathogenesis of rheumatoid arthritis, atherosclerosis, diabetic nephropathy, acute kidney injury, hyperlipidaemia and insulin resistance, autoimmune diseases (including type 1 diabetes mellitus and multiple sclerosis), salt-sensitive hypertension and hepatocellular carcinoma. (nature.com)
  • Systemic lupus erythematosus is characterized by the production of plethora of autoantibodies which potentially drive immune-complex related inflammation in various tissues and organs [ 1 ]. (hindawi.com)
  • 5′-GACGTG-3′) on the promoter region in various target genes ( 1 , 2 ). (spandidos-publications.com)
  • We develop a computational model for the hematopoietic erythroid-myeloid lineage decision, which is determined by a genetic switch involving the genes PU.1 and GATA-1. (lu.se)
  • However, prior to commitment, it has been cells, it is evident that GATA-1 and PU.1 are able to specify observed that many genes are expressed at intermediate or basal erythroid and myeloid cell fates (see [16] and references therein). (lu.se)
  • Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). (biomedcentral.com)
  • Nature Communications 13(1): 4121, July 2022. (upenn.edu)
  • Although HIF-1 has been identified as the critical factor regulating cell responses to hypoxia, the molecular mechanisms supporting the pathological effects of IH remain poorly understood. (ibecbarcelona.eu)
  • This post hoc meta-analysis of BLISS-52 and BLISS-76 explored the relationship between baseline BLyS mRNA/protein levels and/or type 1 IFN-inducible gene signature (IFN-1) and responses to the BLyS-targeting monoclonal antibody belimumab in SLE. (biomedcentral.com)
  • Univariate analysis showed that high HIF-1α TAG mRNA levels correlated with shortened metastasis free survival ( P = 0.01). (biomedcentral.com)
  • An interesting fallout from this architecture is that suppression of the cofactor through external means can lead to a loss of cooperativity, and hence to a primed state for PU.1 and GATA-1. (lu.se)
  • The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. (scielo.br)
  • Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1α and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. (biomedcentral.com)
  • Evidence suggest that a patient's genetic predisposition together with environmental factors, such as exposure to pathogens that exhibit molecular mimicry, disturb immune tolerance ( 4 ). (frontiersin.org)
  • Figure 1: Metabolic reprogramming by the immune system. (nature.com)
  • The local tumour microenvironment is the milieu within which the tumour develops, and includes tumour blood vessels, other cells types (e.g. immune cells, fibroblasts, adipocytes), soluble growth factors and signalling molecules. (otago.ac.nz)