Alpha-lipoic acid suppresses N ε -(carboxymethyl) lysine-induced epithelial mesenchymal transition in HK-2 human renal proximal tubule cells

Mei Chen Lo, Ming Hong Chen, Yu Ting Hsueh, Yung Ting Kuo, Horng Mo Lee

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1387-1397
Number of pages11
JournalFree Radical Research
Volume52
Issue number11-12
DOIs
Publication statusPublished - Dec 2 2018

Keywords

  • EMT
  • HIF-1α
  • mitochondria
  • N -(carboxymethyl) lysine
  • TWIST

ASJC Scopus subject areas

  • Biochemistry

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