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Macrophage migration inhibitory factor (MIF) acetylation protects neurons from ischemic injury.


ABSTRACT: Ischemia-induced neuronal death leads to serious lifelong neurological deficits in ischemic stroke patients. Histone deacetylase 6 (HDAC6) is a promising target for neuroprotection in many neurological disorders, including ischemic stroke. However, the mechanism by which HDAC6 inhibition protects neurons after ischemic stroke remains unclear. Here, we discovered that genetic ablation or pharmacological inhibition of HDAC6 reduced brain injury after ischemic stroke by increasing macrophage migration inhibitory factor (MIF) acetylation. Mass spectrum analysis and biochemical results revealed that HDAC6 inhibitor or aspirin treatment promoted MIF acetylation on the K78 residue. MIF K78 acetylation suppressed the interaction between MIF and AIF, which impaired MIF translocation to the nucleus in ischemic cortical neurons. Moreover, neuronal DNA fragmentation and neuronal death were impaired in the cortex after ischemia in MIF K78Q mutant mice. Our results indicate that the neuroprotective effect of HDAC6 inhibition and aspirin treatment results from MIF K78 acetylation; thus, MIF K78 acetylation may be a therapeutic target for ischemic stroke and other neurological diseases.

SUBMITTER: Hu JX 

PROVIDER: S-EPMC9117661 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Macrophage migration inhibitory factor (MIF) acetylation protects neurons from ischemic injury.

Hu Jin-Xia JX   Ma Wei-Jing WJ   He Li-Ying LY   Zhang Cong-Hui CH   Zhang Cheng C   Wang Yan Y   Chen Chao-Nan CN   Shen Da-Yong DY   Gao Hui-Min HM   Guo Rui-Ru RR   Ning Qian-Qian QQ   Ye Xin-Chun XC   Cui Gui-Yun GY   Li Lei L  

Cell death & disease 20220518 5


Ischemia-induced neuronal death leads to serious lifelong neurological deficits in ischemic stroke patients. Histone deacetylase 6 (HDAC6) is a promising target for neuroprotection in many neurological disorders, including ischemic stroke. However, the mechanism by which HDAC6 inhibition protects neurons after ischemic stroke remains unclear. Here, we discovered that genetic ablation or pharmacological inhibition of HDAC6 reduced brain injury after ischemic stroke by increasing macrophage migrat  ...[more]

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