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The Neurovascular Protective Effect of S14G‐Humanin in a Murine MCAO Model and Brain Endothelial Cells
Author(s) -
Peng Tao,
Wan Wencui,
Wang Jingtao,
Liu Yu,
Fu Zhenqiang,
Ma Xingrong,
Li Junmin,
Sun Guifang,
Ji Yangfei,
Lu Jingjing,
Lu Hong,
Liu Yufeng
Publication year - 2018
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1869
Subject(s) - neuroprotection , pharmacology , cell adhesion molecule , in vivo , microbiology and biotechnology , chemistry , biology
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