Abstract
Beta-hydroxybutyric acid (BHB) exerts a protective effect in experimental of kidney disease models. However, the mechanisms underlying this activity are not well defined. BHB stands out for its ability to inhibit the Nε-lysine acetylation of histone and non-histone proteins, which may affect cellular processes and protein functions. In adriamycin-injured murine glomerular podocytes, BHB ameliorates podocyte damage and preserves actin cytoskeleton integrity, reminiscent of the effect of MS275, a highly selective inhibitor of lysine deacetylase. Further research found that adriamycin causes the reduced acetylation of nephrin, WT-1, and GSK3β. This process is abrogated by the lysine deacetylase inhibitor or BHB, suggesting that the acetylation of these molecules regulates their activity. In contrast, anacardic acid, a selective inhibitor of acetyltransferase, decreases the acetylation of nephrin, WT-1, and GSK3β and mitigates the podocyte protective effects of BHB. Taken together, BHB attenuates adriamycin-elicited glomerular epithelial cell injury, at least in part, by inhibiting the deacetylation of the key molecules implicated in glomerular injury.