title: Dehydroepiandrosterone prevents linoleic acid-induced endothelial cell senescence by increasing autophagy.
abstract: BACKGROUND
  Autophagy has emerged as a potentially important factor in the pathogenesis of atherosclerosis. Dehydroepiandrosterone (DHEA) is an adrenal steroid of great recent interest due to its anti-aging and anti-atherogenic effects; however, little is known about its role in autophagy and endothelial senescence.
  
  
  OBJECTIVE
  The aim of this study was to investigate whether DHEA prevents linoleic acid (LA)-induced endothelial senescence by enhancing autophagy.
  
  
  METHODS
  After pre-treatement with or without DHEA prior to LA treatment in human aortic endothelial cells (HAECs), the level of senescence was compared by senescence-associated acidic β-galactosidase (SA-β-Gal) staining and hyperphosphorylated pRB (ppRB) protein level. Autophagy was detected by LC3 conversion and measuring the level of p62/SQSTM1 (sequestosome 1), a protein degraded by autophagy. The fusion of autophagosome and lysosome was confirmed by fluorescence microscopy.
  
  
  RESULTS
  Pre-treatment with DHEA inhibited LA-induced endothelial senescence. DHEA increased the conversion of LC3-I to LC3-II and decreased the level of p62 in a time- and dose-dependent manner. Although both DHEA and LA treatment increased the conversion of LC3-I to LC3-II, treatment of LA increased p62 and decreased fusion of autophagosome and lysosome, which reflected decreased autophagic flux. However, pre-treatment with DHEA restored autophagic flux inhibited by LA. When we evaluated signaling pathways, we found that JNK activation involved in LC3 conversion induced by DHEA.
  
  
  CONCLUSIONS
  DHEA prevents LA-induced endothelial senescence by restoring autophagy and autophagic flux through JNK activation.
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Jeju National University Hospital, Jeju National School of Medicine, Jeju, Republic of Korea.
authors.forename: Sang Ah
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Jung
authors.affiliation: Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Hae Kyeong
authors.initials: HK
authors.lastname: Yoon
authors.affiliation: Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: So Mi
authors.initials: SM
authors.lastname: Seol
authors.affiliation: Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoo La
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: lwjatlas@amc.seoul.kr.
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: jypark@amc.seoul.kr.
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000494:pharmacology; D019787:Linoleic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008247:Lysosomes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010588:Phagosomes / Q000378:metabolism; D034741:RNA, Small Interfering; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D003687:Dehydroepiandrosterone; D019787:Linoleic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D001616:beta-Galactosidase
keywords: Aging; Atherosclerosis; Autophagy; Dehydroepiandrosterone; Endothelial cells