Phenazine Methosulfate Decreases HIF-1α Accumulation during the Exposure of Cells to Hypoxia
Phenazine Methosulfate Decreases HIF-1α Accumulation during the Exposure of Cells to Hypoxia
复制标题
吩嗪硫酸甲酯可减少细胞缺氧期间 HIF-1α 的积累
DOI：
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
H. Muratsubaki
中科院分区：
文献类型：
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作者：
A. Yamaki;H. Muratsubaki
在HEK 293细胞中，暴露于各种NAD（P）H氧化剂，包括吩嗪硫酸甲酯（PMS），其非酶促氧化细胞内NAD（P）H为NAD（P），减少缺氧诱导的缺氧诱导因子1（HIF-1α）积累。RT-PCR和放线菌酮抑制实验表明，PMS诱导的HIF-1α表达降低与低氧时HIF-1α的翻译后降解有关。蛋白酶体抑制剂MG 132不能消除PMS引起的HIF-1α的降低。此外，在常氧条件下单独暴露于MG 132诱导的HIF-1α增加被PMS减弱。相比之下，钙蛋白酶抑制剂钙蛋白酶抑制素肽完全阻止了PMS诱导的缺氧细胞中HIF-1α的减少。这些数据表明，PMS诱导的HIF-1α稳定性降低是由于PMS激活了一个不依赖于泛素-蛋白酶体途径的蛋白降解系统。
In HEK293 cells, exposure to various NAD(P)H oxidants, including phenazine methosulfate (PMS), that non-enzymatically oxidize intracellular NAD(P)H to NAD(P), decreased hypoxia-induced hypoxia-inducible factor 1 (HIF-1α) accumulation. RT-PCR and cycloheximide inhibition experiments indicated that PMS-induced HIF-1α decrease is involved in post-translational degradation during hypoxia. The decrease in HIF-1α caused by PMS was not eliminated by proteasome inhibitor MG132. Moreover, the increase in HIF-1α induced by exposure to MG132 alone in normoxia was diminished by PMS. In contrast, calpastatin peptide, a calpain inhibitor, fully prevented PMS-induced reduction in HIF-1α in hypoxic cells. These data suggest that the decreased stability of HIF-1α induced by PMS is due to the activation by PMS of a protein degradation system that is independent of the ubiquitin-proteasome pathway.
DOI：
10.1073/pnas.92.12.5510
发表时间：
1995-06-06
影响因子：
11.1
作者：
WANG, GL;JIANG, BH;SEMENZA, GL
通讯作者：
SEMENZA, GL
影响因子：
5.5
作者：
Wheaton, William W.;Chandel, Navdeep S.
通讯作者：
Chandel, Navdeep S.