Genotoxic effects of 1-nitropyrene in macrophages are mediated through a p53-dependent pathway involving cytochrome c release, caspase activation, and PARP-1 cleavage

doi:10.1016/j.ecoenv.2021.112062

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24024

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24024

Title:	Genotoxic effects of 1-nitropyrene in macrophages are mediated through a p53-dependent pathway involving cytochrome c release, caspase activation, and PARP-1 cleavage
Authors:	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
Keywords:	1-Nitropyrene;Genotoxicity;p53-dependent pathway;Macrophage
Date:	2021
Issue Date:	2022-08-05T09:46:38Z (UTC)
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN:	0147-6513
Abstract:	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
Relation:	ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY ,2021,v213
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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