Acetyl-l-carnitine prevents homocysteine-induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells

Molecular Medicine Reports
Shui-Ping YangGuo-Ping Cao

Abstract

Previous studies have revealed that high levels of serum homocysteine (Hcy) are closely associated with the development of juvenile and age-related cataracts. An increased concentration of Hcy is likely to induce gene specific demethylation in DNA promoter regions. The aim of the present study was to prevent this demethylation by administering acetyl-l-carnitine (ALCAR) to human lens epithelial cells (HLECs). Different concentrations of Hcy were used to treat HLECs for 3, 6, 12 and 24 h and the findings were used to determine the optimum dose to induce endoplasmic reticulum (ER) stress. Similarly, the concentration of ALCAR was standardized. The production of reactive oxygen species (ROS) and the percentage of cells undergoing cell death were measured. The levels of antioxidants, ER stress-associated proteins, mRNA levels of nuclear factor erythroid-2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1) and promoter DNA methylation of the Keap1 gene were also assessed. Hcy was observed to induce ER stress, produce ROS and lead to cell death. However, administration of ALCAR prevented these effects to a significant degree. Additionally, western blot analysis revealed that ALCAR increased the levels of antioxidant...Continue Reading

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Citations

May 6, 2017·Oxidative Medicine and Cellular Longevity·Shehzad BatliwalaIok-Hou Pang
May 16, 2019·Neurology. Neuroimmunology and Neuroinflammation·Arie R GafsonPaul M Matthews
Feb 7, 2019·Journal of Complementary & Integrative Medicine·Amany M HegazyAmal S Abdel-Azeem
Apr 11, 2020·Oxidative Medicine and Cellular Longevity·Ming-Xuan WangYa-Juan Zheng
Aug 3, 2021·Experimental Eye Research·Tayler F L WishartFrank J Lovicu

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