期刊
RESEARCH AND REPORTS IN BIOCHEMISTRY
卷 5, 期 -, 页码 147-161出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/RRBC.S58280
关键词
HIF; nitric oxide; Cco/NO mitochondrial signaling; ROS/RNS; cancer
资金
- National Institutes of Health [30228]
Hypoxia-inducible factor-1 (HIF-1) is responsible for cellular adaptations to hypoxia. While oxygen (O-2) negatively regulates its stability, many other factors affect HIF-1 stability and activity, including nitric oxide (NO). NO derived from l-arginine and nitrite (NO2-) could nitrosylate or nitrate HIF-1 and multiple proteins involved in HIF-1 regulation, and can allow HIF-1 to escape normoxic degradation. In turn, HIF-1 can increase NO production through multiple mechanisms, including increased inducible nitric oxide synthase (iNOS) expression and subunit 4-2 of cytochrome c oxidase (COX4-2) expression. There is therefore a high degree of crosstalk between HIF-1 and NO signaling. As such, many cellular responses to NO are mediated by HIF-1, and vice versa. This includes, but is not limited to, angiogenesis, apoptosis, senescence, and metabolic changes. These pathways all have important functions in normal physiology and when altered can contribute or, in some cases, lead to pathogenesis.
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