Mitochondrial oxidative damage and apoptosis induced by high glucose through Rho kinase signal pathway in renal tubular epithelial cells

• Published in: Asian Pacific Journal of Tropical Medicine
• Main Authors: Wen-Ning Li, Hui Han, Zi-Yang Jing, Xiao-Hong Yang, Yin Zhang, Jia-Li Wei
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wolters Kluwer Medknow Publications 2018
• Subjects: diabetic nephropathy; mitochondrial oxidative stress; rho kinase signal pathway; tubular epithelial cell; Arctic medicine. Tropical medicine; RC955-962; Arctic; Rho
• Online Access: https://doi.org/10.4103/1995-7645.234769; https://doaj.org/article/21f2e3c5f67c4a45a170569c3b71740a

Objective: To investigate the role of oxidative stress in human renal tubular epithelial cells (HK-2) induced by high glucose and the underlying signal pathway in vitro. Methods: MYPT1, pro-caspase-3, PGC-1α, and Drp1 protein expressions were measured by Western blot. MnSOD2, Drp1 and PGC-1α mRNA expressions were detected by real time PCR. Results: Results showed that high glucose significantly up-regulated the protein expressions of MYPT1, pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells; while Rho kinase inhibitor fasudil and ROCK1 siRNA inhibited protein expressions of pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells induced by high glucose. Importantly, fasudil and ROCK1 siRNA markedly inhibited the expressions of mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α in HK-2 cells induced by high glucose. Conclusions: Our findings suggest that Rho kinase signal pathway is involved in mitochondrial oxidative damage and apoptosis in high glucose-induced renal tubular epithelial cells by regulating mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α. Targeting Rho kinase signal pathway might be a potential strategy for the treatment of diabetic nephropathy.