title: Aldose reductase in keratinocytes attenuates cellular apoptosis and senescence induced by UV radiation.
abstract: Although aldose reductase (AR) has been implicated in the cellular response to oxidative stress, the role of AR in ultraviolet-B (UVB)-induced cellular injury has not been investigated. Here, we show that an increased expression of AR in human keratinocytes modulates UVB-induced apoptotic cell death and senescence. Overexpression of AR in HaCaT cells significantly attenuated UVB-induced cellular damage and apoptosis, with a decreased generation of reactive oxygen species (ROS) and aldehydes. Ablation of AR with small interfering RNA or inhibition of AR activity abolished these effects. We also show that increased AR activity suppressed UVB-induced activation of the p38 and c-Jun N-terminal kinases, but did not affect the extracellular signal-regulated kinase and phosphatidylinositol 3-kinase pathways. Similarly, UVB-induced translocation of Bax and Bcl-2 to mitochondria and cytosol, respectively, was markedly attenuated in cells overexpressing AR. Knockdown or inhibition of AR activity in primary cultured keratinocytes enhanced UVB-induced cellular senescence and increased the level of a cell-cycle regulatory protein, p53. Finally, cellular apoptosis induced by UVB radiation was significantly reduced in the epidermis of transgenic mice overexpressing human AR. These findings suggest that AR plays an important role in the cellular response to oxidative stress by sequestering ROS and reactive aldehydes generated in keratinocytes.
authors.affiliation: Department of Pharmacology, Gyeongsang Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kang
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iwata
authors.forename: Kanako
authors.initials: K
authors.lastname: Ikami
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Ham
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Jae Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Soo-Bong
authors.initials: SB
authors.lastname: Park
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yabe-Nishimura
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
mesh_terms: D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D016922:Cellular Senescence; D004817:Epidermis / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D020935:MAP Kinase Signaling System; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013471:Sunburn / Q000378:metabolism / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000447:Aldehydes; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D051028:bcl-2-Associated X Protein; D000449:Aldehyde Reductase; D058539:Phosphatidylinositol 3-Kinase