RT Journal Article
SR Electronic
T1 Lactate-derived HDAC6 Lactylation as a new target for neuronal protection in cerebral ischemic reperfusion injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.27.518054
DO 10.1101/2022.11.27.518054
A1 Cao, Jun
A1 Hong, Zexuan
A1 Zeng, Fanning
A1 Qin, Zaisheng
A1 Lin, Miao
A1 Wang, Hao
A1 Zuo, Daming
A1 Tao, Tao
YR 2022
UL http://biorxiv.org/content/early/2022/11/27/2022.11.27.518054.abstract
AB Lactylation is a newly found lactate-derived post-translational modification, which is firstly reported on histone protein lysine residues to regulate gene expression. Here, we provided evidence that higher serum lactate level was possibly associated with better prognosis in ischemic stroke patients. Meanwhile, inhibition of endogenous lactate increased the infarct volume and decreased protein pan-lactylation in the affected brain tissue in cerebral ischemia mice. We further demonstrated that downregulating lactylation level of Hdac6 (Histone Deacetylase 6) in neurons exacerbated ischemic neuronal injury. The underlying mechanisms involved Hdac6 lactylation disturbing calcium homeostasis through binding BiP (Binding immunoglobulin protein), an endoplasmic reticulum-related protein. Collectively, our findings identified a new effect of lactate for neuroprotection through Hdac6 lactylation during cerebral ischemic reperfusion injury which introduced a potential therapeutic approach against ischemic stroke.Competing Interest StatementThe authors have declared no competing interest.