l-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury.

Autor: Cheng J; Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan 430060, China., Tang JC; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Pan MX; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Chen SF; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Zhao D; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Zhang Y; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Liao HB; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Zhuang Y; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Lei RX; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Wang S; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Liu AC; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Chen J; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, 185 Donghu Street, Wuhan 430071, China., Zhang ZH; Department of Neurology, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan 430060, China., Li HT; Institute of Neuroregeneration & Neurorehabilitation, Department of Neurosurgery & Pathophysiology, Qingdao University, 308 Ningxia Street, Qingdao 266071, China., Wan Q; Institute of Neuroregeneration & Neurorehabilitation, Department of Neurosurgery & Pathophysiology, Qingdao University, 308 Ningxia Street, Qingdao 266071, China. Electronic address: qwanwh@hotmail.com., Chen QX; Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan 430060, China. Electronic address: chenqx666@whu.edu.cn.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2020 May; Vol. 327, pp. 113214. Date of Electronic Publication: 2020 Jan 24.
DOI: 10.1016/j.expneurol.2020.113214
Abstrakt: l-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how l-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that l-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that l-lysine may play a neuroprotective role in ICH injury. Indeed, we show that l-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. l-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of l-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of l-lysine in ICH injury. Together, our results suggest that l-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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