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

Authors :
Chang, Chun-Yu
Shen, Chao-Yu
Kang, Chao-Kai
Sher, Yuh-Pyng
Sheu, Wayne H.-H.
Chang, Chia-Che
Lee, Tsung-Han
Source :
Toxicology & Applied Pharmacology. Sep2014, Vol. 279 Issue 3, p351-363. 13p.
Publication Year :
2014

Abstract

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 that 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0041008X
Volume :
279
Issue :
3
Database :
Academic Search Index
Journal :
Toxicology & Applied Pharmacology
Publication Type :
Academic Journal
Accession number :
98400564
Full Text :
https://doi.org/10.1016/j.taap.2014.06.029