Ets-1 as an early response gene against hypoxia-induced apoptosis in pancreatic β-cells.

摘要: Hypoxia complicates islet isolation for transplantation and may contribute to pancreatic β-cell failure in type 2 diabetes. Pancreatic β-cells are susceptible hypoxia-induced apoptosis. Severe hypoxic conditions during the immediate post-transplantation period a main non-immune factor leading death graft failure. In this study, we identified transcription Ets-1 (v-ets erythroblastosis virus E26 oncogene homolog 1) as an early response gene against apoptosis β-cells. regulates at multiple levels according degree of oxygen deprivation. Moderate hypoxia promotes transcription, whereas severe its transactivation activity, well ubiquitin-proteasome mediated degradation. This degradation causes relative insufficiency limits effect on downstream hypoxic-inducible genes anti-apoptotic function. Overexpression ectopic MIN6 INS-1 cells protects them from mitochondria-dependent manner, confirming that sufficient amount activity is critical protection injury. Targeting expression be useful strategy period.