A Dual Role of ATM in Ischemic Preconditioning and Ischemic Injury.

Abstract:

:The ataxia-telangiectasia mutated (ATM) protein is regarded as the linchpin of cellular defenses to stress. Deletion of ATM results in strong oxidative stress and degenerative diseases in the nervous system. However, the role of ATM in neuronal ischemic preconditioning and lethal ischemic injury is still largely unknown. In this study, mice cortical neurons preconditioned with sublethal exposure to oxygen glucose deprivation (OGD) exhibited ATM/glucose-6-phosphate dehydrogenase pathway activation. Additionally, pharmacological inhibition of ATM prior to the preconditioning reversed neuroprotection provided by preconditioning in vitro and in vivo. Meanwhile, we found that ATM/P53 pro-apoptosis pathway was driven by lethal OGD injury, and pharmacological inhibition of ATM during fatal oxygen-glucose deprivation/reperfusion injury promoted neuronal survival. More importantly, inhibition of ATM activity after cerebral ischemia protected against cerebral ischemic-reperfusion damage in mice. In conclusion, our data show the dual role of ATM in neuronal ischemic preconditioning and lethal ischemic injury, involving in the protection of ischemic preconditioning, but promoting neuronal death in lethal ischemic injury. Thus, the present study provides new opportunity for the treatment of ischemic stroke.

journal_name

Cell Mol Neurobiol

authors

Xie GH,Dai HJ,Liu F,Zhang YP,Zhu L,Nie JJ,Wu JH

doi

10.1007/s10571-019-00773-6

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

785-799

issue

5

eissn

0272-4340

issn

1573-6830

pii

10.1007/s10571-019-00773-6

journal_volume

40

pub_type

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