Alpha-lipoic acid suppresses Nε-(carboxymethyl) lysine-induced epithelial mesenchymal transition in HK-2 human renal proximal tubule cells. (2nd December 2018)

• Record Type: Journal Article
• Authors: Lo, Mei-Chen; Chen, Ming-Hong; Hsueh, Yu-Ting; Kuo, Yung-Ting; Lee, Horng-Mo
• Is Part Of: Free radical research. Volume 52:Number 11/12(2018)
• Page Start: 1387
• Page End: 1397
• Publication Date: 2018-12-02
• Subjects: EMT -- HIF-1α -- mitochondria -- Nε-(carboxymethyl) lysine -- TWIST; Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.1080/10715762.2018.1489129
• Languages: English
• ISSNs: 1071-5762

Abstract

Abstract: N ε -(carboxymethyl) lysine (CML) plays causal roles in diabetic complications. In the present study, we investigated whether CML-induced HIF-1α accumulation and epithelial-mesenchymal transition (EMT) in HK-2 renal proximal tubular epithelial cells. Treatment with CML-BSA increased reactive oxygen species (ROS) production reduced the mitochondrial membrane potential and induced mitochondrial fragmentation. Pre-treatment of cells with antioxidant, α-lipoic acid, normalised the ROS production and restored the mitochondrial membrane potential. These changes were accompanied with morphological changes of epithelial mesenchymal transition. CML-BSA increased the protein level of hypoxia-inducible factor-1α (HIF-1α), and the EMT-associated transcription factor, TWIST. These effects were reversed by α-lipoic acid. CML-BSA increased the protein levels of mesenchymal-specific markers, including vimentin, α-smooth muscle actin, which were alleviated by pre-treatment with α-lipoic acid. Our data suggest that CML-BSA induces EMT through a ROS/HIF-1α/TWIST-dependent mechanism, and that α-lipoic acid may alleviate the CML-induced EMT in renal tubular cells.