Add like
Add dislike
Add to saved papers

Lactate dehydrogenase A mediated histone lactylation induced the pyroptosis through targeting HMGB1.

Cerebral ischemia (CI), as the cerebrovascular disease with the highest incidence rate, is treated by limited intravenous thrombolysis and intravascular therapy to recanalize the embolized vessels. Recently, the discovery of histone lactylation proposes a potential molecular mechanism for the role of lactate in physiological and pathological processes. This study aimed to analyze the lactate dehydrogenase A (LDHA) mediated histone lactylation in CI reperfusion (CI/R) injury. Oxygen-glucose deprivation/reoxygenation (OGD/R) treated N2a cells and middle cerebral artery occlusion (MCAO) treated rats was used as the CI/R model in vivo and in vitro. Cell viability and pyroptosis was assessed using CCK-8 and flow cytometry. RT-qPCR was performed to detect the relative expression. The relationship between histone lactylation and HMGB1 was verified by CHIP assay. LDHA, HMGB1, lactate and histone lactylation was up-regulated in the OGD/R treated N2a cells. Additionally, LDHA knockdown decreased HMGB1 levels in vitro, and relieved CI/R injury in vivo. Besides, LDHA silencing declined the histone lactylation mark enrichment on HMGB1 promoter, and lactate supplement rescued it. What?s more, LDHA knockdown decreased the IL-18 and IL-1β contents, and the cleaved-caspase-1 and GSDMD-N protein levels in the OGD/R treated N2a cells, which was reversed by HMGB1 overexpression. Knockdown of LDHA suppressed the pyroptosis in the N2a cells induced by OGD/R, which was reversed by HMGB1 overexpression. Mechanistically, LDHA mediated the histone lactylation induced pyroptosis through targeting HMGB1 in the CI/R injury.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

Related Resources

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app