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Title: Taurine protects HK-2 cells from oxidized LDL-induced cytotoxicity via the ROS-mediated mitochondrial and p53-related apoptotic pathways

Oxidized LDL (oxLDL) induces a pro-oxidative environment and promotes apoptosis, causing the progression of renal diseases in humans. Taurine is a semi-essential amino acid in mammals and has been shown to be a potent endogenous antioxidant. The kidney plays a pivotal role in maintaining the balance of taurine. However, the mechanisms underlying the protective effects of taurine against oxLDL-induced injury in renal epithelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effects of taurine on human proximal tubular epithelial (HK-2) cells exposed to oxLDL and explored the related mechanisms. We observed that oxLDL increased the contents of ROS and of malondialdehyde (MDA), which is a lipid peroxidation by-product that acts as an indicator of the cellular oxidation status. In addition, oxLDL induced cell death and apoptosis in HK-2 cells. Pretreatment with taurine at 100 μM significantly attenuated the oxLDL-induced cytotoxicity. We determined that oxLDL triggered the phosphorylation of ERK and, in turn, the activation of p53 and other apoptosis-related events, including calcium accumulation, destabilization of the mitochondrial permeability and disruption of the balance between pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins. The malfunctions induced by oxLDL were effectively blocked by taurine. Thus, our results suggested thatmore » taurine exhibits potential therapeutic activity by preventing oxLDL-induced nephrotoxicity. The inhibition of oxLDL-induced epithelial apoptosis by taurine was at least partially due to its anti-oxidant activity and its ability to modulate the ERK and p53 apoptotic pathways. - Highlights: • Oxidized LDL induced cytotoxicity and apoptosis in HK-2 cells. • Pretreatment with taurine attenuated oxLDL-induced nephrotoxicity. • Taurine protected against renal damages through inhibition of ROS generation. • Taurine prevented apoptosis through modulation of the p53 phosphorylation.« less
Authors:
 [1] ;  [2] ;  [3] ;  [3] ;  [4] ;  [5] ;  [3] ;  [1] ;  [3] ;  [3] ;  [3] ;  [1] ;  [3] ;  [4] ;  [3] ;  [3] ;  [3]
  1. Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China)
  2. School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan (China)
  3. (China)
  4. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, (China)
  5. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan (China)
Publication Date:
OSTI Identifier:
22439833
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 279; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALKOXY RADICALS; AMINO ACIDS; ANTIOXIDANTS; APOPTOSIS; CALCIUM; CATALASE; GLUTATHIONE; HYDROXYL RADICALS; KIDNEYS; MITOCHONDRIA; OXYGEN; PERMEABILITY; PHOSPHORYLATION; STRESSES; SUPEROXIDE DISMUTASE; SUPEROXIDE RADICALS; TAURINE; TOXICITY