PT  - JOURNAL ARTICLE
AU  - Cao, Jun
AU  - Hong, Zexuan
AU  - Zeng, Fanning
AU  - Qin, Zaisheng
AU  - Lin, Miao
AU  - Wang, Hao
AU  - Zuo, Daming
AU  - Tao, Tao
TI  - Lactate-derived HDAC6 Lactylation as a new target for neuronal protection in cerebral ischemic reperfusion injury
AID  - 10.1101/2022.11.27.518054
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.27.518054
4099  - http://biorxiv.org/content/early/2022/11/27/2022.11.27.518054.short
4100  - http://biorxiv.org/content/early/2022/11/27/2022.11.27.518054.full
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.