Essential role of Nrf2 in keratinocyte protection from UVA by quercetin.
Much of the cell injury caused by ultraviolet A (UVA) irradiation is associated with oxidative stress. Quercetin is a major natural polyphenol that is known to protect cells from UVA-induced damage. Here, we investigated the molecular mechanism of this protection. Quercetin pretreatment strongly suppressed UVA-induced apoptosis in human keratinocyte HaCaT cells, markedly increased protein levels of the transcription factor Nrf2, induced the expression of antioxidative genes, and dramatically reduced the production of reactive oxygen species following UVA irradiation. Importantly, these beneficial effects were greatly attenuated by downregulating Nrf2 expression. Thus, quercetin protects cells from UVA damage mainly by elevating intracellular antioxidative activity via the enhanced accumulation of a transcription factor for antioxidant genes, Nrf2.
Kimura
Shintarou
S
Majors of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Warabi
Eiji
E
Yanagawa
Toru
T
Ma
Dongmei
D
Itoh
Ken
K
Ishii
Yoshiyuki
Y
Kawachi
Yasuhiro
Y
Ishii
Tetsuro
T
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000502:physiology*; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D020218:Response Elements; D014466:Ultraviolet Rays / Q000009:adverse effects
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D011794:Quercetin