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Macrophage migration inhibitory factor (MIF) acetylation protects neurons from ischemic injury.
- Source :
-
Cell death & disease [Cell Death Dis] 2022 May 18; Vol. 13 (5), pp. 466. Date of Electronic Publication: 2022 May 18. - Publication Year :
- 2022
-
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.<br /> (© 2022. The Author(s).)
- Subjects :
- Acetylation
Animals
Aspirin pharmacology
Histone Deacetylase 6 metabolism
Humans
Mice
Intramolecular Oxidoreductases genetics
Intramolecular Oxidoreductases metabolism
Ischemic Stroke genetics
Ischemic Stroke metabolism
Ischemic Stroke pathology
Macrophage Migration-Inhibitory Factors genetics
Macrophage Migration-Inhibitory Factors metabolism
Nervous System Diseases metabolism
Nervous System Diseases pathology
Neurons metabolism
Neurons pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 13
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 35585040
- Full Text :
- https://doi.org/10.1038/s41419-022-04918-2