Mitochondrial Dysfunction Enhances Susceptibility to Oxidative Stress by Down-Regulation of Thioredoxin in Human Neuroblastoma Cells |
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Authors: | Hongqun Ding Jing Gao Zengrong Zhu Yuyun Xiong Jiankang Liu |
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Institution: | (1) School of Pharmacy, Jiangsu University, Zhenjiang, 212013, P.R. China;(2) State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, 210093, P.R. China;(3) Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697-4540, USA |
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Abstract: | Increasing evidence suggests that Alzheimer’s disease is associated with mitochondrial dysfunction and oxidative damage. To
develop a cellular model of Alzheimer’s disease, we investigated the effects of thioredoxin (Trx) expression in the response
to mitochondrial dysfunction-enhanced oxidative stress in the SH-SY5Y human neuroblastoma cells. Treatment of SH-SY5Y cells
with 15 mM of NaN3, an inhibitor of cytochrome c oxidase (complex IV), led to alteration of mitochondrial membrane potential but no significant changes in cell viability.
Therefore, cells were first treated with 15 mM NaN3 to induce mitochondrial dysfunction, then, exposed to different concentrations of H2O2. Cell susceptibility was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and morphological
observation. Expressions of Trx mRNA and protein were determined by RT-PCR; and Western-blot analysis, respectively. It was
found that the SH-SY5Y cells with mitochondrial impairment had lower levels of Trx mRNA and protein, and were significantly
more vulnerable than the normal cells after exposure to H2O2 while no significant changes of Trx mRNA and protein in SH-SY5Y cells exposed to H2O2 but without mitochondrial complex IV inhibition. These results, together with our previous study in primary cultured neurons,
demonstrated that the increased susceptibility to oxidative stress is induced at least in part by the down-regulation of Trx
in SH-SY5Y human neuroblastoma cells with mitochondrial impairment and also suggest the mitochondrial dysfunction-enhanced
oxidative stress could be used as a cellular model to study the mechanisms of Alzheimer’s disease and agents for prevention
and treatment. |
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Keywords: | Sodium azide Hydrogen peroxide Oxidative stress Thioredoxin Cell susceptibility SH-SY5Y human neuroblastoma cells |
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