Hypoxia-inducible factor-1alpha, a key factor in the keratinocyte response to UVB exposure.
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-1alpha expression in keratinocytes. We found that UVB induces a biphasic HIF-1alpha variation through reactive oxygen species (ROS) generation. Whereas rapid production of cytoplasmic ROS down-regulates HIF-1alpha 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-1alpha phosphorylation and accumulation after UVB irradiation. Our experiments also revealed a key role of HIF-1alpha 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.
Rezvani
Hamid Reza
HR
Inserm U876, University Bordeaux, and Centre Hospitalier Universitaire de Bordeaux, France.
Dedieu
Sophie
S
North
Sophie
S
Belloc
Francis
F
Rossignol
Rodrigue
R
Letellier
Thierry
T
de Verneuil
Hubert
H
Taïeb
Alain
A
Mazurier
Frédéric
F
D017209:Apoptosis / Q000528:radiation effects*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000528:radiation effects*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D011499:Protein Processing, Post-Translational / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases