UV radiation-mediated photodamage to the skin has been implicated in premature aging and photoaging-related skin cancer and melanoma. Little is known about the cellular events that underlie premature senescence, or how to impede these events. In the present study we demonstrate that PPARδ (peroxisome-proliferator-activated receptor δ) regulates UVB-induced premature senescence of normal keratinocytes. Activation of PPARδ by GW501516, a specific ligand of PPARδ, significantly attenuated UVB-mediated generation of ROS (reactive oxygen species) and suppressed senescence of human keratinocytes. Ligand-activated PPARδ up-regulated the expression of PTEN (phosphatase and tensin homologue deleted on chromosome 10) and suppressed the PI3K (phosphatidylinositol 3-kinase)/Akt pathway. Concomitantly, translocation of Rac1 to the plasma membrane, which leads to the activation of NADPH oxidases and generation of ROS, was significantly attenuated. siRNA (small interfering RNA)-mediated knockdown of PTEN abrogated the effects of PPARδ on cellular senescence, on PI3K/Akt/Rac1 signalling and on generation of ROS in keratinocytes exposed to UVB. Finally, when HR-1 hairless mice were treated with GW501516 before exposure to UVB, the number of senescent cells in the skin was significantly reduced. Thus ligand-activated PPARδ confers resistance to UVB-induced cellular senescence by up-regulating PTEN and thereby modulating PI3K/Akt/Rac1 signalling to reduce ROS generation in keratinocytes.
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Research Article|
April 26 2012
Ligand-activated PPARδ inhibits UVB-induced senescence of human keratinocytes via PTEN-mediated inhibition of superoxide production
Sun Ah Ham;
Sun Ah Ham
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Jung Seok Hwang;
Jung Seok Hwang
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Taesik Yoo;
Taesik Yoo
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Hanna Lee;
Hanna Lee
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Eun Sil Kang;
Eun Sil Kang
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Chankyu Park;
Chankyu Park
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Jae-Wook Oh;
Jae-Wook Oh
†Division of Animal Life Science, Kon-Kuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Hoon Taek Lee;
Hoon Taek Lee
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Gyesik Min;
Gyesik Min
‡Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology, Jinju 660-758, Republic of Korea
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Jin-Hoi Kim;
Jin-Hoi Kim
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
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Han Geuk Seo
Han Geuk Seo
1
*Department of Animal Biotechnology, Konkuk University, Gwangjin-Gu, Seoul 143-701, Republic of Korea
1To whom correspondence should be addressed (email hgseo@konkuk.ac.kr).
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Publisher: Portland Press Ltd
Received:
October 14 2011
Revision Received:
February 13 2012
Accepted:
February 16 2012
Accepted Manuscript online:
February 16 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 444 (1): 27–38.
Article history
Received:
October 14 2011
Revision Received:
February 13 2012
Accepted:
February 16 2012
Accepted Manuscript online:
February 16 2012
Citation
Sun Ah Ham, Jung Seok Hwang, Taesik Yoo, Hanna Lee, Eun Sil Kang, Chankyu Park, Jae-Wook Oh, Hoon Taek Lee, Gyesik Min, Jin-Hoi Kim, Han Geuk Seo; Ligand-activated PPARδ inhibits UVB-induced senescence of human keratinocytes via PTEN-mediated inhibition of superoxide production. Biochem J 15 May 2012; 444 (1): 27–38. doi: https://doi.org/10.1042/BJ20111832
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