Hydrogen sulfide protects SH-SY5Y neuronal cells against d-galactose induced cell injury by suppression of advanced glycation end products formation and oxidative stress |
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Authors: | Yan-Ying Liu Bhushan Vijay NagpurePeter T-H Wong Jin-Song Bian |
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Institution: | Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore |
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Abstract: | d-Galactose is widely used as an agent to cause aging effects in experimental animals. The present study aims to investigate the effects of hydrogen sulfide (H2S) in human neuroblastoma SH-SY5Y cells exposed to d-galactose. Cells were pretreated with NaHS, an H2S donor, and then exposed to d-galactose (25–400 mM for 48 h). We found that NaHS pretreatment significantly reversed the d-galactose-induced cell death and cellular senescence. MTT assay shows that NaHS significantly increased cell viability from 62.31 ± 1.29% to 72.34 ± 0.46% compared with d-galactose (200 mM) treatment group. The underlying mechanism appeared to involve a reduction by NaHS in the formation of advanced glycation end products (AGEs), which are known to contribute to the progression of age-related diseases. In addition, NaHS decreased the elevation of reactive oxygen species from 151.17 ± 2.07% to 124.8 ± 2.89% and malondialdehyde from 1.72 ± 0.07 to 1.10 ± 0.08 (nmol/mg protein) in SH-SY5Y cells after d-galactose exposure. NaHS also stimulated activities of superoxide dismutase from 0.42 ± 0.05 to 0.73 ± 0.04 (U/mg protein) and glutathione peroxidase from 3.98 ± 0.73 to 14.73 ± 0.77 (nmol/min/mg protein) and upregulated the gene expression levels of copper transport protein ATOX1, glutathione synthetase (GSS) and thioredoxin reductase 1 (TXNRD1) while down-regulated aldehyde oxidase 1 (AOX1). In summary, our data indicate that H2S may have potentially anti-aging effects through the inhibition of AGEs formation and reduction of oxidative stress. |
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Keywords: | H2S hydrogen sulfide AGEs advanced glycation end products GSS glutathione synthetase TXNRD1 thioredoxin reductase 1 AOX1 aldehyde oxidase 1 MDA malondialdehyde SOD superoxide dismutase GPx glutathione peroxidase ATOX1 ATX1 antioxidant protein 1 MTT 3-[4 5-dimethylthiazol-2-yl]-2 5-diphenyltetrazolium bromide LDH lactate dehydrogenase RAGE receptors for AGEs ROS reactive oxygen species DCF 2&rsquo 7&rsquo -dichlorofluorescin |
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