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Factor HIF-1 (factor + hif-1)
Kinds of Factor HIF-1 Selected AbstractsCorrelation of hypoxic signalling to histological grade and outcome in cartilage tumoursHISTOPATHOLOGY, Issue 5 2010Stephane Boeuf Boeuf S, Bovée J V M G, Lehner B, Hogendoorn P C W & Richter W (2010) Histopathology56, 641,651 Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours Aims:, The molecular mechanisms underlying the progression of central chondrosarcoma are so far poorly understood. The aim of this study was to identify genes involved in the progression of these tumours by comparison of gene expression and correlation of expression profiles to histological grade and clinical outcome. Methods and results:, Array-based gene expression profiling of 19 chondrosarcoma samples was performed. Beside differences in the expression of cartilage matrix molecules, high-grade chondrosarcoma showed enhanced expression of the matrix metalloproteinase MMP-2 and of the hypoxia-inducible molecule galectin 1. Immunohistochemical analysis of galectin 1 and of further hypoxia-associated proteins was performed on 68 central and peripheral tumour samples. Hypoxia-inducible factor 1, (HIF-1,) activation was significantly elevated in high-grade central chondrosarcoma. A negative correlation of carbonic anhydrase IX expression to metastasis-free survival was independent of histological grade. Conclusions:, The expression patterns identified in this study point towards a substantial role for angiogenic and hypoxic signalling in chondrosarcoma progression. The constitutive activation of the transcription factor HIF-1, in high-grade chondrosarcoma could play a central role in the regulation of cell metabolism and vascularization in these tumours and may, for this reason, represent a potential target for chondrosarcoma therapy. [source] Selective induction of mucin-3 by hypoxia in intestinal epitheliaJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2006Nancy A. Louis Abstract Epithelial cells line mucosal surfaces (e.g., lung, intestine) and critically function as a semipermeable barrier to the outside world. Mucosal organs are highly vascular with extensive metabolic demands, and for this reason, are particularly susceptible to diminished blood flow and resultant tissue hypoxia. Here, we pursue the hypothesis that intestinal barrier function is regulated in a protective manner by hypoxia responsive genes. We demonstrate by PCR confirmation of microarray data and by avidin blotting of immunoprecipitated human Mucin 3 (MUC3), that surface MUC3 expression is induced in T84 intestinal epithelial cells following exposure to hypoxia. MUC3 RNA is minimally detectable while surface protein expression is absent under baseline normoxic conditions. There is a robust induction in both the mRNA (first evident by 8 h) and protein expression, first observed and maximally expressed following 24 h hypoxia. This is followed by a subsequent decline in protein expression, which remains well above baseline at 48 h of hypoxia. Further, we demonstrate that this induction of MUC3 protein is associated with a transient increase in the barrier restorative peptide, intestinal trefoil factor (ITF). ITF not only colocalizes with MUC3, by confocal microscopy, to the apical surface of T84 cells following exposure to hypoxia, but is also found, by co-immunoprecipitation, to be physically associated with MUC3, following 24 h of hypoxia. In exploration of the mechanism of hypoxic regulation of mucin 3 expression, we demonstrated by luciferase assay that the full-length promoter for mouse Mucin 3 (Muc3) is hypoxia-responsive with a 5.08,±,1.76-fold induction following 24 h of hypoxia. Furthermore, analysis of both the human (MUC3A) and mouse (Muc3) promoters revealed potential HIF-1 binding sites which were shown by chromatin immunoprecipitation to bind the pivotal hypoxia-regulating transcription factor HIF-1,. Taken together, these studies implicate the HIF-1, mediated hypoxic induced expression of mucin 3 and associated ITF in the maintenance of intestinal barrier function under hypoxic conditions. J. Cell. Biochem. 99: 1616,1627, 2006. © 2006 Wiley-Liss, Inc. [source] Up-regulation of heat shock protein HSP 20 in the hippocampus as an early response to hypoxia of the newbornJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Jean-Claude David Abstract Hypoxia is an important challenge for newborn mammals. Stress generated at the brain level under low oxygenation conditions results in up-regulation of heat shock proteins (HSPs) and other stress proteins. The aim of the present work was to determine the effect of hypoxia in the newborn on some newly described small molecular weight HSPs (HSP 20 and B8) in the hippocampus, cortex and cerebellum of newborn piglets. These effects will be compared with those of other closely related proteins such as ,B crystallin, HSP 27, heme oxygenase (HO)-1, HO-2, cyclooxygenase (COX)-1 and COX-2. The piglets were submitted to hypoxia (5% O2; 95% N2) over either 1 or 4 h, with recovery periods ranging from 0 to 68 h. Western blot analysis showed that HSP 20 was rapidly induced only in the hippocampus, long before hypoxia-inducible transcription factor HIF-1,, while HSP 27 was rapidly induced in the cortex and cerebellum. Vascular epithelial growth factor was increased simultaneously in the three regions. Moreover, an increase in the expression of, respectively, HO-1 and COX-2 was observed later, but at the same time, in the three regions tested. It appears that HSP 20 can be an early marker of hypoxia in the hippocampus. The other small HSPs or stress proteins display different temporal patterns of up-regulation (HSP 27 and HO-1, COX-2) or do not show changes in their expressions (,B crystallin, HSP B8, HO-2 and COX-1). [source] Melatonin modulates the expression of VEGF and HIF-1, induced by CoCl2 in cultured cancer cellsJOURNAL OF PINEAL RESEARCH, Issue 2 2008Min Dai Abstract:, Melatonin is an important natural oncostatic agent. At present there are no data available as to its possible influence on tumor angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. It is well known that vascular endothelial growth factor (VEGF) is crucial to a solid tumor's higher vascularization and development. To investigate the possible influence of melatonin on angiogenesis, we studied the effect of melatonin on endogenous VEGF expression in three human cancer cell lines (PANC-1, HeLa and A549 cells). In this study, we report that physiologic concentrations of melatonin have no obvious impact on the VEGF expression, whereas pharmacologic concentrations of melatonin suppress the VEGF mRNA and protein levels induced by hypoxia mimetic cobalt chloride (CoCl2). Melatonin also decreases hypoxia-inducible factor (HIF)-1, protein levels, suggesting a role for transcription factor HIF-1 in the suppression of VEGF expression. The effect of pharmacologic concentrations of melatonin on VEGF and HIF-1, under normoxia is uncertain, which indicates that the regulatory mechanisms of VEGF in the absence or presence of CoCl2 are different and other or additional transcription factors may be involved. Taken together, our data show that melatonin in high concentrations markedly reduces the expression of endogenous VEGF and HIF-1, induced by CoCl2 in cultured cancer cells. [source] Altered expression of mRNA for HIF-1, and its target genes RTP801and VEGF in patients with oral lichen planusORAL DISEASES, Issue 3 2010M Ding Oral Diseases (2010) 16, 299,304 Objective:, To explore a potential causal contribution of the transcription factor HIF-1, and its target gene, RTP801 and VEGF, to the development of oral lichen planus (OLP). Design relevant:, Twenty-two adult OLP patients were enrolled in this study. All OLP diagnoses were verified by histopathological characteristics. Normal mucous specimens were collected from 12 controls after various oral surgeries. Material and method:, RNA was isolated from OLP and control specimens. Microarray was performed using BiostarH-40s gene chip. Expression of HIF-1,, VEGF and RTP801 was evaluated using quantitative real-time polymerase chain reaction (qPCR). Unpaired t -test and one-way ANOVA was used for statistical analysis. Results:, Microarray results showed that RTP801 expression was lower in OLP than in controls (779 vs 3090). qPCR further confirmed that expression of RTP801 was similarly lower in OLP than in controls (0.363 vs 1.473, P < 0.001); expression of VEGF was also lower in OLP (0.448 vs 1.74, P = 0.012). In contrast, expression of HIF-1, was higher in OLP than in controls (11.12 vs 1.628, P < 0.001). Conclusion:, The oral mucosa of OLP is hypoxic. Genes that are activated by hypoxia, such as RTP801 and VEGF, and their signal cascades may be novel potential therapeutic targets for OLP. [source] Organ preservation solutions attenuate accumulation and nuclear translocation of hypoxia-inducible factor-1, in the hepatoma cell line HepG2CELL BIOCHEMISTRY AND FUNCTION, Issue 8 2009Renate Paddenberg Abstract Hypoxia-inducible factor-1, (HIF-1,) is a key transcription factor orchestrating hypoxic and inflammatory reactions. Here, we determined the impact of organ preservation solutions (Celsior; histidine-tryptophan-ketoglutarate solution, HTK; University of Wisconsin solution; UW), oxygen supply, and temperature on HIF-1, accumulation, recorded by Western blotting and immunocytochemistry, in the human hepatoma cell line HepG2. Generation of reactive oxygen species (ROS), NO, and cell viability were concomitantly assessed. At 4°C, HIF-1, accumulation was not detectable. In normothermic (37°C) cell culture medium (Dulbecco's Modified Eagle's Medium, DMEM), HepG2 cells accumulated HIF-1, even in normoxia (21% O2) which was not observed in either of the preservation solutions. This correlated to high generation of NO, a normoxic stabilizer of HIF-1,, and L -arginine content (substrate for NO synthesis) in DMEM, and low NO production and absence of L -arginine in preservation solutions. In normothermic hypoxia up to 24,h, intracellular HIF-1, accumulated in all conditions, but less in preservation solutions compared to DMEM. The inhibitory effect on accumulation and nuclear translocation was most prominent for HTK, the only solution containing the activator of HIF-1, degradation, , -ketoglutarate. Addition of other intermediates of the tricarbon acid cycle,succinate, fumarate, malate,did not alter HIF-1, accumulation, although succinate exhibited a beneficial effect on cell viability in cold storage. In conclusion, preservation solutions attenuate accumulation and nuclear translocation of the transcription factor HIF-1,, and this property is seemingly related to their chemical composition (L -arginine, , -ketoglutarate). Thus, it appears feasible to design preservation solution specifically to modify HIF-1, accumulation and nuclear translocation. Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||