Tauroursodeoxycholic Acid Attenuates Apoptosis Mediated by High-Concentration Glucose in Proximal Tubular Cells

Abstract

Background: Tauroursodeoxycholic acid (TUDCA) treatment significantly decreases the blood sugar content and exerts renoprotective effects in db/db mice. These changes are likely related to endoplasmic reticulum (ER) stress and apoptosis inhibition. Purpose: To elucidate the mechanism underlying the association between the renoprotective effect of TUDCA and ER stress inhibition. Methods: Renal proximal tubular cells (HK-2 (Human Kidney-2) cells) were cultured with or without TUDCA (0.1, 0.2, and 0.4 mmol/L) in normal or high-concentration glucose (HG) media. After 48 h, we determined the HK-2 apoptosis and proliferation rates by flow cytometry and methyl thiazol tetrazolium (MTT) assay, respectively. Furthermore, we detected intracellular reactive oxygen species (ROS) levels and the mitochondrial membrane potential per group. Finally, we analyzed the expression of ER stress-related markers using western blotting and real-time polymerase chain reaction. Results: TUDCA treatment protected HK-2 cells from HG damage, reduced apoptosis, and restored cell proliferation inhibited by HG through the ER stress pathway. The protective effect on HK-2 cells corresponded with ROS inhibition and mitochondrial membrane potential stabilization. Additionally, TUDCA treatment downregulated CCAAT enhancer binding protein (C/EBP) homologous protein (i.e., CHOP) and glucose-regulated protein: 78 kDa (i.e., GRP78) expression, which were upregulated in the HG group. Conclusions: Our results suggest that TUDCA protected renal proximal tubular cells against HG-induced apoptosis by suppressing ER stress.