Suppression of HDAC2 by sodium butyrate alleviates apoptosis of kidney cells in db/db mice and HG-induced NRK-52E cells

Abstract

Butyrate is short-chain fatty acid, which is produced by intestinal microbiota metabolizing dietary fibers. Butyrate participates in various physiological processes predominantly by activating G-coupled-receptors, inhibiting histone deacetylases (HDACs) and serving as an energy substrate. Previous studies have shown that butyrate plays a protective role in diabetic nephropathy (DN); however, the exact mechanism remains unclear. The present study identified that providing sodium butyrate (NaBu) by gavage relieved renal damage and apoptosis in db/db mice, which is a widely used type 2 DN model. In vitro, NaBu suppressed high glucose (HG)-induced apoptosis in normal rat kidney tubular epithelial (NRK-52E) cells. Of the eleven HDACs (HDAC1-11) studied, only the mRNA expression of HDAC2 was attenuated by NaBu in NRK-52E cells under the HG condition. Overexpression of HDAC2 offset the anti-apoptotic effect of NaBu. NaBu also suppressed HG-induced oxidative stress. Additionally, H2O2 induced an upregulation of HDAC2 in NRK-52E cells, while NaBu inhibited this process. Mechanistically, NaBu acted as an antioxidant in HG-induced NRK-52E cells and suppressed HG-induced apoptosis of NRK-52E cells through inhibiting HDAC2 by virtue of its anti-oxidative property.