Search results for "Hypoxia-inducible factors"
showing 6 items of 16 documents
Nitric oxide, derived from inducible nitric oxide synthase, decreases hypoxia inducible factor-1α in macrophages during aspirin-induced mesenteric in…
2010
Background and purpose: Nitric oxide (NO) modulates expression of hypoxia inducible factor-1 (HIF-1), a transcription factor regulating function of myeloid cells. Here, we have assessed the role played by NO, formed by inducible NOS (iNOS), in the inflammation induced by aspirin in the gut, by modulating HIF-1 activity. Experimental approach: The role of iNOS-derived NO on leucocyte–endothelial interactions induced by aspirin was evaluated by intravital microscopy in mesenteric venules of rats pretreated with selective iNOS inhibitors, 1400W or l-N6-(1-iminoethyl)-lysine. NO was localized by fluorescence microscopy, using DAF-FM. iNOS, HIF-1α and CD36 were localized by immunohistochemistr…
Hypoxia inducible factor-1alpha inactivation unveils a link between tumor cell metabolism and hypoxia-induced cell death.
2008
Hypoxia and the acquisition of a glycolytic phenotype are intrinsic features of the tumor microenvironment. The hypoxia inducible factor-1alpha (HIF-1alpha) pathway is activated under hypoxic conditions and orchestrates a complex transcriptional program that enhances cell survival. Although the consequences of HIF-1alpha inactivation in cancer cells have been widely investigated, only a few studies have addressed the role of HIF-1alpha in the survival of cancer cells endowed with different glycolytic capacities. In this study, we investigated this aspect in ovarian cancer cells. Hypoxia-induced toxicity was increased in highly glycolytic cells compared with poorly glycolytic cells; it was a…
Role of reactive oxygen species in the regulation of HIF-1 by prolyl hydroxylase 2 under mild hypoxia
2012
The function and survival of eukaryotic cells depends on a constant and sufficient oxygen supply. Cells recognize and respond to hypoxia by accumulation of the transcription factor hypoxia-inducible factor 1 (HIF-1), composed of an oxygen-sensitive HIF-1α and a constitutive HIF-1β subunit. Besides physiology, HIF-1 induction is involved in major pathological processes such as cardiovascular disease, inflammation and cancer, which are associated with the formation of reactive oxygen species (ROS). ROS have been reported to affect HIF-1 activity but the role for ROS in regulating HIF-1 has not been definitely settled. In order to shed light on the redox-regulation of HIF-1 by ROS, we studied …
Hypoxia-inducible factor 1Α may regulate the commitment of mesenchymal stromal cells toward angio-osteogenesis by mirna-675-5P
2017
Abstract Background aims During bone formation, angiogenesis and osteogenesis are regulated by hypoxia, which is able to induce blood vessel formation, as well as recruit and differentiate human mesenchymal stromal cells (hMSCs). The molecular mechanisms involved in HIF-1α response and hMSC differentiation during bone formation are still unclear. This study aimed to investigate the synergistic role of hypoxia and hypoxia-mimetic microRNA miR-675-5p in angiogenesis response and osteo-chondroblast commitment of hMSCs. Methods By using a suitable in vitro cell model of hMSCs (maintained in hypoxia or normoxia), the role of HIF-1α and miR-675-5p in angiogenesis and osteogenesis coupling was inv…
The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral s…
2012
Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to suc…
Hypoxia Positively Regulates the Expression of pH-Sensing G-Protein–Coupled Receptor OGR1 (GPR68)
2016
Background & Aims: A novel family of proton-sensing G-proteinâcoupled receptors, including ovarian cancer G-proteinâcoupled receptor 1 (OGR1) (GPR68) has been identified to play a role in pH homeostasis. Hypoxia is known to change tissue pH as a result of anaerobic glucose metabolism through the stabilization of hypoxia-inducible factor-1α. We investigated how hypoxia regulates the expression of OGR1 in the intestinal mucosa and associated cells. Methods: OGR1 expression in murine tumors, human colonic tissue, and myeloid cells was determined by quantitative reverse-transcription polymerase chain reaction. The influence of hypoxia on OGR1 expression was studied in monocytes/macrophages and…