Abstract
Endothelial dysfunction is fundamental to ischemic stroke and brain injury. The humanin analogue S14G-humanin (HNG) has been shown to be a cytoprotective derivative. In this study, we investigated the neuroprotective effects of HNG in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, HNG ameliorates cerebral infarction and suppresses the production of TNF-α, IL-1β, IL-6 and MCP-1 cytokines. HNG inhibits the expression of vascular adhesion molecules such as VCAM-1 and ICAM-1 in the cortex tissue. In mouse brain endothelial cells bEnd.3, HNG protects cell survival under oxygen deprivation (OGD) conditions. HNG suppresses ROS production as well as that of the same panel of cytokines and vascular adhesion molecules induced by OGD. HNG also reduces the numbers of THP-1 cells attached to bEnd.3 by OGD. Mechanistically, we show that HNG exerts its effect via inhibition of the NF- κB pathway factor IKKα, activation of IκBα and accumulation of p65 in the nucleus. Our data conclude that S14G-humanin serves as a neuroprotective factor, especially in brain vascular disorders. © 2018 IUBMB Life, 70(7):691-699, 2018.
References
Jan 1, 1989·Stroke; a Journal of Cerebral Circulation·E Z LongaR Cummins
May 7, 2003·Nature·Bin GuoJohn C Reed
Jul 16, 2003·Peptides·Yohichi YamagishiIkuo Nishimoto
May 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guoguang YingJi Ming Wang
Nov 6, 2004·Journal of Peptide Science : an Official Publication of the European Peptide Society·Gabriela KrejcovaJirina Slaninova
May 26, 2005·Pharmacological Reviews·Brian T Hawkins, Thomas P Davis
Apr 28, 2006·Journal of Human Genetics·Tesseki KinSatoshi Ueno
Sep 9, 2006·Stroke; a Journal of Cerebral Circulation·Xingshun XuBalvin H L Chua
Jul 2, 2008·Brain Research·Xingshun XuBalvin H L Chua
Apr 22, 2009·Biochemistry·Sara PistolesiRebecca Pogni
Apr 24, 2009·Molecular Biology of the Cell·Yuichi HashimotoMasaaki Matsuoka
Jun 22, 2010·Cardiovascular Research·Adi R BacharAmir Lerman
Nov 26, 2010·Pharmacological Reports : PR·Barbara ZapałaAldona Dembińska-Kieć
Jul 19, 2011·Atherosclerosis·Yun K OhAmir Lerman
Sep 22, 2011·Neurochemical Research·Shen-Ting ZhaoYa Ke
Feb 14, 2012·PloS One·David G ZachariasAmir Lerman
Oct 2, 2013·Blood·Longbiao YaoRodger P McEver
Dec 3, 2014·Diabetes Research and Clinical Practice·Ying XieChun-Feng Liu
Sep 19, 2015·Endocrinology·YanHe LueChristina Wang
Oct 16, 2015·Stroke; a Journal of Cerebral Circulation·Andrea Kassner, Zamir Merali
Jul 8, 2016·Oncotarget·Su-Jeong KimKelvin Yen
Jul 20, 2017·Neurological Research·Guangsheng GaoYun Li
Jul 21, 2017·Cell Death & Disease·Sonali NashineM Cristina Kenney
Dec 6, 2017·Oxidative Medicine and Cellular Longevity·A Tressera-RimbauA Vallverdú-Queralt
Citations
Dec 26, 2018·Expert Opinion on Therapeutic Targets·Camila Florencia ZuccatoMarianela Candolfi
May 16, 2019·Stroke; a Journal of Cerebral Circulation·Yupei ShenXu Chen
Oct 5, 2021·Bioengineered·Ping ZhangShuai Li