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Behav Brain Res. 2020 Jan 29:112520. doi: 10.1016/j.bbr.2020.112520. [Epub ahead of print]

H2S prevents injury after ischemic stroke by diminishing the assembly of CaMKII with ASK1-MKK3-p38 signaling module.

Author information

1
Department of Genetics, Research Center for Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China; Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China.
2
Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China; School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China.
3
Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China; Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China.
4
School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China.
5
Department of Human Anatomy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China.
6
School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China. Electronic address: mantang567@163.com.
7
School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, PR China. Electronic address: xunbz@163.com.

Abstract

Cerebral ischemia/reperfusion (I/R) injury is a leading cause of learning and memory dysfunction. Hydrogen sulfide (H2S) has been shown to confer neuroprotection in various neurodegenerative diseases, including cerebral I/R-induced hippocampal CA1 injury. However, the underlying mechanisms have not been completely understood. In the present study, rats were pretreated with SAM/NaHS (SAM, an H2S agonist, and NaHS, an H2S donor) only or SAM/NaHS combined with CaM (an activator of CaMKII) prior to cerebral ischemia. The Morris water maze test demonstrated that SAM/NaHS could alleviate learning and memory impairment induced by cerebral I/R injury. Cresyl violet staining was used to show the survival of hippocampal CA1 pyramidal neurons. SAM/NaHS significantly increased the number of surviving cells, whereas CaM weakened the protection induced by SAM/NaHS. The immunohistochemistry results indicated that the number of Iba1-positive microglia significantly increased after cerebral I/R. Compared with the I/R group, the number of Iba1-positive microglia in the SAM/NaHS groups significantly decreased. Co-Immunoprecipitation and immunoblotting were conducted to demonstrate that SAM/NaHS suppressed the assembly of CaMKII with the ASK1-MKK3-p38 signal module after cerebral I/R, which decreased the phosphorylation of p38. In contrast, CaM significantly inhibited the effects of SAM/NaHS. Taken together, the results suggested that SAM/NaHS could suppress cerebral I/R injury by downregulating p38 phosphorylation via decreasing the assembly of CaMKII with the ASK1-MKK3-p38 signal module.

KEYWORDS:

ASK1-MKK3-p38; CaMKII; H(2)S; SAM; ischemia/reperfusion

PMID:
32006563
DOI:
10.1016/j.bbr.2020.112520

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