Oncotarget

Research Papers: Pathology:

Hydrogen sulfide ameliorates subarachnoid hemorrhage-induced neuronal apoptosis via the ROS-MST1 pathway

Ligen Shi, Jianwei Lei, Hangzhe Xu, Jingwei Zheng, Yan Wang, Yucong Peng, Jun Yu _ and Jianmin Zhang

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Oncotarget. 2017; 8:73547-73558. https://doi.org/10.18632/oncotarget.20569

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Abstract

Ligen Shi1,*, Jianwei Lei1,*, Hangzhe Xu1, Jingwei Zheng1, Yan Wang1, Yucong Peng1, Jun Yu1 and Jianmin Zhang1,2,3

1 Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

2 Brain Research Institute, Zhejiang University, Hangzhou, Zhejiang, China

3 Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, China

* These authors have contributed equally to this work

Correspondence to:

Jun Yu, email:

Jianmin Zhang, email:

Keywords: hydrogen sulfide, MST1, neuronal apoptosis, subarachnoid hemorrhage, early brain injury, Pathology Section

Received: July 03, 2017 Accepted: August 08, 2017 Published: August 28, 2017

Abstract

Background: Hydrogen sulfide (H2S) has shown a neuroprotective role in several cerebrovascular diseases. This study aimed to explore the underlying mechanisms of H2S in early brain injury after subarachnoid hemorrhage (SAH).

Methods: One hundred seventy-seven male Sprague-Dawley rats were employed in this study. Sodium hydrosulfide (NaHS), a donor of H2S, was injected intraperitoneally at 60 min after SAH was induced by endovascular perforation. Western blot analysis determined the expression of several proteins of interest, and an immunofluorescence assay was used to examine neuronal apoptosis.

Results: Exogenous NaHS markedly improved neurological scores, attenuated brain edema, and ameliorated neuronal apoptosis at 24 h after SAH induction. The underlying mechanisms of H2S in ameliorating neuronal apoptosis might be executed through inhibition of the activity of mammalian sterile 20-like kinase 1 (MST1) protein. Western blot analysis demonstrated that exogenous NaHS decreased cleaved MST1 (cl-MST1) while increasing full-length MST1 expression. This anti-apoptotic effect of H2S could be reversed by chelerythrine, which could activate MST1 via caspase-dependent cleavage.

Conclusions: Exogenous NaHS, as a donor of H2S, could ameliorate early brain injury after SAH by inhibiting neuronal apoptosis by reducing the activity of the MST1 protein.


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