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Regulation of lactate production through p53/β-enolase axis contributes to statin-associated muscle symptoms

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johan
(@j)
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Findings
Blood lactate levels of mice treated with lovastatin increased 23% compared to the control group, which was reproduced in type II predominant glycolytic muscles, accompanied with a 23.1% decrease of maximum swim duration time. The in vitro evidence revealed that statins increased the expression of muscle specific glycolytic enzyme β-enolase through promoting the degradation of basal p53 proteins, resulting in increased of lactate production. Co-administered with dichloroacetate (DCA), a reagent effective in treating lactic acidosis, reverted the elevated lactate levels and the decreased exercise capacity.

Interpretation
Elevated lactate production by statins through the p53/β-enolase axis contributes to SAMS.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642070/


   
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medline
(@aliml2)
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Statins also increase intracellular lactate by inhibiting the monocarboxylate transporter (MCT4), so they acidify both intracellular and extracellular!

https://europepmc.org/article/med/26521871


   
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