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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on March 4, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/gln055
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Induction of Cellular Senescence by Secretory Phospholipase A2 in Human Dermal Fibroblasts through an ROS-Mediated p53 Pathway

Hyun Jung Kim, Kwang Seok Kim, Si Hyung Kim, Suk-Hwan Baek, Hwa Young Kim, ChuHee Lee and Jae-Ryong Kim

Department of Biochemistry and Molecular Biology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, Republic of Korea

Address correspondence to Jae-Ryong Kim, MD, PhD, Department of Biochemistry and Molecular Biology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong, Daegu 705-717, Republic of Korea. Email: kimjr{at}ynu.ac.kr


  Abstract

Secretory phospholipase A2 (sPLA2) is involved in various cellular physiological and pathological responses, especially in inflammatory responses. Accumulating evidence suggests that inflammation is an underlying basis for the molecular alterations that link aging and age-related pathological processes. However, the involvement of sPLA2 in cellular senescence is not clear. In this study, we found that sPLA2 treatment induces cellular senescence in human dermal fibroblasts (HDFs), as confirmed by increases in senescence-associated β-galactosidase activity, changes in cell morphology, and upregulation of p53/p21 protein levels. sPLA2-induced senescence was observed in p16-knockdown HDFs and p16-null mouse fibroblasts, but not in p53-knockdown HDFs and p53-null mouse fibroblasts. Treatment with sPLA2 increases reactive oxygen species (ROS) production, and an antioxidant, N-acetylcysteine, inhibits sPLA2-induced cellular senescence. These results suggest that sPLA2 has a role in cellular senescence in HDFs during inflammatory response by promoting ROS-dependent p53 activation and might therefore contribute to inflammatory disorders associated with aging.

Keywords Cell aging; Secretory PLA2; Inflammation; p53; ROS

Received: May 19, 2008; Accepted: October 12, 2008

Decision Editor: Huber R. Warner, PhD


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