Chang Ming-Yang, Chang Si-Yuan, Su Pei-Pei, Tian Fei, Liu Zhang-Suo
Department of Nephrology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan Province, P. R. China.
Department of Surgical Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan Province, P. R. China.
Am J Transl Res. 2021 Aug 15;13(8):8847-8859. eCollection 2021.
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.
β-羟基丁酸（BHB）在实验性肾脏疾病模型中发挥保护作用。然而，这种活性背后的机制尚未完全明确。BHB因其抑制组蛋白和非组蛋白蛋白质的Nε-赖氨酸乙酰化的能力而引人注目，这可能会影响细胞过程和蛋白质功能。在阿霉素损伤的小鼠肾小球足细胞中，BHB可改善足细胞损伤并维持肌动蛋白细胞骨架的完整性，这让人联想到赖氨酸脱乙酰酶的高度选择性抑制剂MS275的作用效果。进一步研究发现，阿霉素会导致nephrin、WT-1和GSK3β的乙酰化减少。赖氨酸脱乙酰酶抑制剂或BHB可消除这一过程，表明这些分子的乙酰化调节其活性。相反，乙酰转移酶的选择性抑制剂漆树酸会降低nephrin、WT-1和GSK3β的乙酰化，并减弱BHB对足细胞的保护作用。综上所述，BHB至少部分地通过抑制与肾小球损伤相关的关键分子的脱乙酰化来减轻阿霉素引起的肾小球上皮细胞损伤。
