title: Taurine protects HK-2 cells from oxidized LDL-induced cytotoxicity via the ROS-mediated mitochondrial and p53-related apoptotic pathways.
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.
authors.affiliation: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chang
authors.affiliation: School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Shen
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chao-Kai
authors.initials: CK
authors.lastname: Kang
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Yuh-Pyng
authors.initials: YP
authors.lastname: Sher
authors.affiliation: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang Ming University, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wayne H-H
authors.initials: WH
authors.lastname: Sheu
authors.affiliation: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan. Electronic address: chia_che@dragon.nchu.edu.tw.
authors.forename: Chia-Che
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan,; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan; Department of Biological Science and Technology, China Medical University, Taichung, Taiwan. Electronic address: thlee@email.nchu.edu.tw.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000975:Antioxidants; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008074:Lipoproteins / Q000302:isolation & purification / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D000975:Antioxidants; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C099252:oxidized low density lipoprotein; D013654:Taurine; D004247:DNA; D013482:Superoxide Dismutase; D053148:Caspase 3
keywords: Apoptosis; HK-2 cells; ROS; Taurine; oxLDL