Agani Faton H, Pichiule Paola, Carlos Chavez Juan, LaManna Joseph C
Department of Anatomy, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4938, USA.
Comp Biochem Physiol A Mol Integr Physiol. 2002 May;132(1):107-9. doi: 10.1016/s1095-6433(01)00535-9.
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that regulates transcriptional activation of several genes that are responsive to oxygen lack, including erythropoietin, vascular endothelial growth factor, various glycolytic enzymes and the GLUT-1 glucose transporter. Because mitochondria have been postulated to be involved in the regulation of HIF-1, we tested the effects of mitochondrial electron transport chain complex I inhibitors, rotenone and 1-methyl-4-phenylpiridinium (MPP(+)), on hypoxic-induced accumulation of HIF-1 alpha, the regulated component of the dimer. We found, consistent with our previous observations in Cath.a and PC12 cells, that rotenone and MPP(+) attenuated the HIF-1 alpha hypoxic response. Thus, it can be concluded that an intact, functional mitochondrial respiratory chain is required for HIF-1 alpha accumulation.
缺氧诱导因子1（HIF-1）是一种异源二聚体转录因子，可调节多个对缺氧有反应的基因的转录激活，包括促红细胞生成素、血管内皮生长因子、各种糖酵解酶和GLUT-1葡萄糖转运蛋白。由于线粒体被推测参与HIF-1的调节，我们测试了线粒体电子传递链复合物I抑制剂鱼藤酮和1-甲基-4-苯基吡啶鎓（MPP(+)）对缺氧诱导的HIF-1α（二聚体的调节成分）积累的影响。我们发现，与我们之前在Cath.a和PC12细胞中的观察结果一致，鱼藤酮和MPP(+)减弱了HIF-1α的缺氧反应。因此，可以得出结论，完整、有功能的线粒体呼吸链是HIF-1α积累所必需的。
