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| 题名: | Genotoxic effects of 1-nitropyrene in macrophages are mediated through a p53-dependent pathway involving cytochrome c release, caspase activation, and PARP-1 cleavage |
| 作者: | Wu, SW;Su, CH;Ho, YC;Huang-Liu, R;Tseng, CC;Chiang, YW;Yeh, KL;Lee, SS;Chen, WY;Chen, CJ;Li, YC;Lee, CY;Kuan, YH |
| 关键词: | 1-Nitropyrene;Genotoxicity;p53-dependent pathway;Macrophage |
| 日期: | 2021 |
| 上传时间: | 2022-08-05T09:46:38Z (UTC)
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| 出版者: | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| ISSN: | 0147-6513 |
| 摘要: | Genotoxic stress from environmental pollutants plays a critical role in cytotoxicity. The most abundant nitropolycyclic aromatic hydrocarbon in environmental pollutants, 1-nitropyrene (1-NP), is generated during fossil fuel, diesel, and biomass combustion under sunlight. Macrophages, the key regulators of the innate immune system, provide the first line of defense against pathogens. The toxic effects of 1-NP on macrophages remain unclear. Through a lactate dehydrogenase assay, we measured the cytotoxicity induced by 1-NP. Our results revealed that 1-NP induced genotoxicity also named DNA damage, including micronucleus formation and DNA strand breaks, in a concentration-dependent manner. Furthermore, 1-NP induced p53 phosphorylation and nuclear accumulation; mitochondrial cytochrome c release; caspase-3 and-9 activation and cleavage; and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage in a concentration-dependent manner. Pretreatment with the PARP inhibitor, 3-aminobenzamide, significantly reduced cytotoxicity, genotoxicity, and PARP-1 cleavage induced by 1-NP. Pretreatment with the caspase-3 inhibitor, z-DEVD-fmk, significantly reduced cytotoxicity, genotoxicity, PARP-1 cleavage, and caspase 3 activation induced by 1-NP. Pretreatment with the p53 inhibitor, pifithrin-?, significantly reduced cytotoxicity, genotoxicity, PARP-1 cleavage, caspase 3 activation, and p53 phosphorylation induced by 1-NP. We propose that cytotoxicity and genotoxicity induced by 1-NP by PARP-1 cleavage via caspase-3 and-9 activation through cytochrome c release from mitochondria and its upstream p53-dependent pathway in macrophages. |
| URI: | http://dx.doi.org/10.1016/j.ecoenv.2021.112062
https://www.webofscience.com/wos/woscc/full-record/WOS:000632392800006
https://ir.csmu.edu.tw:8080/handle/310902500/24024 |
| 關聯: | ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY ,2021,v213 |
| 显示于类别: | [中山醫學大學研究成果] 期刊論文
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