期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 282, 期 22, 页码 16413-16422出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M611397200
关键词
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Hypoxia-inducible factor-1 (HIF-1) is a major transcription factor sensitive to oxygen levels, which responds to stress factors under both hypoxic and nonhypoxic conditions. UV irradiation being a common stressor of skin, we looked at the effect of UVB on HIF-1 alpha expression in keratinocytes. We found that UVB induces a biphasic HIF-1 alpha variation through reactive oxygen species ( ROS) generation. Whereas rapid production of cytoplasmic ROS down-regulates HIF-1 alpha expression, delayed mitochondrial ROS generation results in its up-regulation. Indeed, activation of p38 MAPK and JNK1 mediated by mitochondrial ROS were required for HIF-1 alpha phosphorylation and accumulation after UVB irradiation. Our experiments also revealed a key role of HIF-1 alpha in mediating UVB-induced apoptosis. We conclude that the broad impact of the HIF- 1 transcription factor on gene expression could make it a key regulator of UV-responsive genes and photocarcinogenesis.
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