Hypoxia-Inducible Factor-1α Accumulation in the Rat Brain in Response to Hypoxia and Ischemia is Attenuated During Aging
A common feature of senescent organisms is the decline in their ability to respond to different types of stress such as hypoxia or ischemia. Previously it was reported that aging was associated with a defect in compensatory angiogenesis in response to tissue ischemia. This deficit was associated to a reduction of vascular endothelial growth factor (VEGF) expression, an endothelial-specific mitogen that is essential for angiogenesis during development and adulthood. VEGF as well as other hypoxia-responsive genes share a common regulatory pathway. They are regulated by the transcription factor hypoxia inducible factor-1 (HIF-1), a heterodimeric protein consisting of two subunits, HIF-1a and HIF-113. Both subunits are required for DNA binding and transactivation of target genes. HIF-la is unique to HIF-1 and its expression is primarily regulated by oxygen tension. During normoxia the HIF-la gene is expressed continuously; however, the HIE-la protein is rapidly degraded by the ubiquitin-proteosome system. During hypoxia, degradation of HIF-la is suppressed and thereby it accumulates in the nucleus almost instantly. In contrast, the HIP-113 subunit is constitutively expressed and its levels do not change significantly during hypoxia
KeywordsVascular Endothelial Growth Factor Cardiac Arrest Potassium Chloride Solution Transient Global Ischemia Transient Global Cerebral Ischemia
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