PMID- 28888894 OWN - NLM STAT- MEDLINE DCOM- 20180706 LR - 20231112 IS - 2213-2317 (Electronic) IS - 2213-2317 (Linking) VI - 14 DP - 2018 Apr TI - Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling. PG - 116-125 LID - S2213-2317(17)30561-X [pii] LID - 10.1016/j.redox.2017.08.016 [doi] AB - Coronary artery disease (CAD) is a critical cardiovascular disease and a cause of high morbidity and mortality in this world. Hyperhomocysteinemia (HHcy) has been suggested as a risk factor for CAD. In addition, SIRT1 (sirtuin 1) has been reported to play a protective role in a variety of diseases, especially in the cardiovascular system. The main purpose of this study was to investigate the effects of exercise training on apoptosis and inflammation in HHcy animals. We also tested whether exercise protected against Hhcy-induced dysfunction of endothelium through modulation of SIRT1. C57BL mice (8 in each group) were fed with or without 1% L-methionine (w/w) in water for 4 months to induce HHcy. We found that Hhcy repressed SIRT1 and AMPK expression and increased NADPH oxidase activity. Plasma MDA, endothelium LOX-1 and p-p38 were up-regulated by Hhcy induction. NF-kappaB and it downstream molecules were activated under Hhcy situation, thereby promoting pro-inflammatory responses. Moreover, we also reported that Hhcy caused endothelium apoptosis involving Akt inhibition and mitochondria-dependent apoptotic pathways. Exercise training significantly protected against endothelium from Hhcy caused oxidative injuries. In addition, EX527 (SIRT1 inhibitor) reduced the therapeutic effects by exercise. Our results had indicated that exercise training prevent the development of atherosclerosis through SIRT1 activation and oxidative stress inhibition under Hhcy situation. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Chan, Shih-Hung AU - Chan SH AD - Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Hung, Ching-Hsia AU - Hung CH AD - Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Shih, Jhih-Yuan AU - Shih JY AD - Department of Internal Medicine, Chi-Mei Hospital, Tainan, Taiwan. FAU - Chu, Pei-Ming AU - Chu PM AD - Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan. FAU - Cheng, Yung-Hsin AU - Cheng YH AD - Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. FAU - Lin, Huei-Chen AU - Lin HC AD - Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Physical Therapy, Shu-Zen Junior College of Medicine and Management, Taiwan. FAU - Hsieh, Pei-Ling AU - Hsieh PL AD - Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. FAU - Tsai, Kun-Ling AU - Tsai KL AD - Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: kunlingtsai@mail.ncku.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170824 PL - Netherlands TA - Redox Biol JT - Redox biology JID - 101605639 RN - 0 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) RN - 0 (Carbazoles) RN - 0 (NF-kappa B) RN - 0 (Neuropeptides) RN - 0 (Olr1 protein, mouse) RN - 0 (Rac1 protein, mouse) RN - 0 (Scavenger Receptors, Class E) RN - 4Y8F71G49Q (Malondialdehyde) RN - AE28F7PNPL (Methionine) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.6.3.- (NADPH Oxidase 1) RN - EC 3.5.1.- (Sirtuin 1) RN - EC 3.6.5.2 (rac1 GTP-Binding Protein) SB - IM MH - Animals MH - Atherosclerosis/etiology/prevention & control MH - Carbazoles/pharmacology/therapeutic use MH - Endothelium, Vascular/drug effects/metabolism MH - Hyperhomocysteinemia/chemically induced/complications/drug therapy MH - Male MH - Malondialdehyde/blood MH - Methionine/toxicity MH - Mice MH - Mice, Inbred C57BL MH - NADPH Oxidase 1/antagonists & inhibitors/*metabolism MH - NF-kappa B/metabolism MH - Neuropeptides/metabolism MH - Oxidative Stress/drug effects MH - Physical Conditioning, Animal MH - Scavenger Receptors, Class E/*metabolism MH - Signal Transduction/drug effects MH - Sirtuin 1/antagonists & inhibitors/*metabolism MH - Superoxide Dismutase/blood MH - Up-Regulation/drug effects MH - rac1 GTP-Binding Protein/metabolism PMC - PMC5596261 OTO - NOTNLM OT - Coronary artery disease OT - Hyperhomocysteinemia OT - Oxidative stress OT - Sirtuin 1 EDAT- 2017/09/11 06:00 MHDA- 2018/07/07 06:00 PMCR- 2017/08/24 CRDT- 2017/09/11 06:00 PHST- 2017/07/28 00:00 [received] PHST- 2017/08/18 00:00 [revised] PHST- 2017/08/23 00:00 [accepted] PHST- 2017/09/11 06:00 [pubmed] PHST- 2018/07/07 06:00 [medline] PHST- 2017/09/11 06:00 [entrez] PHST- 2017/08/24 00:00 [pmc-release] AID - S2213-2317(17)30561-X [pii] AID - 10.1016/j.redox.2017.08.016 [doi] PST - ppublish SO - Redox Biol. 2018 Apr;14:116-125. doi: 10.1016/j.redox.2017.08.016. Epub 2017 Aug 24.