期刊
TOXICOLOGY LETTERS
卷 296, 期 -, 页码 73-81出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2018.07.047
关键词
Antimony; SIRT1; Apoptosis; ROS; Pulmonary toxicity
类别
资金
- National Natural Science Foundation of China [81703255, 21607082, 81502803]
- Natural Science Foundation of Jiangsu Province [BK20160414]
- Nantong Jiangsu scientific research project [MS12017014-8]
- Natural Science Research Program of Jiangsu Province [15KJB330005]
- National Undergraduate Innovation Experiment Project [201810304107X]
Antimony (Sb) has been reported to lead to pulmonary damage, but the underlying mechanism remains unclear. Accumulating evidence indicates that silent mating type information regulation 2 homolog 1 (SIRT1), an NAD(+)-dependent deacetylase, mediates stimuli-induced cellular apoptosis. Here, we investigated whether SIRT1 plays a role in Sb-triggered apoptosis in human bronchial epithelial cells (BEAS-2b). First, we showed that Sb initiated apoptosis. Furthermore, the expression of SIRT1 was markedly downregulated by Sb treatment, while overexpression of SIRT1 through resveratrol treatment or transfection with SIRT1-Flag plasmid attenuated the Sb-induced apoptosis. Accelerated degradation of SIRT1 protein and lower SIRT1 gene expression contributed to low expression of SIRT1. In addition, Sb activated the ERK and JNK pathways; however, inhibition of ERK rather than JNK rescued SIRT1 suppression. Subsequent analyses demonstrated that antioxidant N-acetylcysteine (NAC) attenuated SIRT1 repression, increased SIRT1 mRNA levels and decreased SIRT1 protein degradation in Sb-treated cells. In addition, NAC also inhibited JNK and ERK activation by Sb exposure. These data suggest that reactive oxygen species-dependent SIRT1 suppression mediates Sb-stimulated cell apoptosis in BEAS-2b cells via lower SIRT1 gene expression and protein stability.
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