Cytotoxic effects of cadmium and zinc co-exposure in PC12 cells and the underlying mechanism

Rahman, Md. Mostafizur; Ukiana, Junki; Uson-Lopez, Rachael; Sikder, Md. Tajuddin; Saito, Takeshi; Kurasaki, Masaaki

Cytotoxic effects of cadmium and zinc co-exposure in PC12 cells and the underlying mechanism

Rahman, Md. Mostafizur; Ukiana, Junki; Uson-Lopez, Rachael et al.

Chemico-Biological Interactions, 2018, 269, 41-49

Permalink : https://hdl.handle.net/2115/68652

このアイテムのアクセス数:978件（2026-08-08 10:41 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/68652
タイトル	Cytotoxic effects of cadmium and zinc co-exposure in PC12 cells and the underlying mechanism
著者	Rahman, Md. Mostafizur ; Ukiana, Junki ; Uson-Lopez, Rachael ; Sikder, Md. Tajuddin ; Saito, Takeshi ; Kurasaki, Masaaki
著者名 Rahman, Md. Mostafizur
著者名 Ukiana, Junki
著者名 Uson-Lopez, Rachael
著者名 Sikder, Md. Tajuddin
e-Rad_Researcher 40153811 著者名 Saito, Takeshi
e-Rad_Researcher 80161727 著者名 Kurasaki, Masaaki
言語	英語
キーワード	apoptosis
	heavy metals
	cytochrome c
	DNA
	caspase 9
	glutathione
発行日	2018-04-02
収録物名	Chemico-Biological Interactions
巻(号)	269
ページ	41-49
抄録	Cadmium (Cd2+) is a well studied inducer of cellular necrosis and apoptosis. Zinc (Zn2+) is known to inhibit apoptosis induced by toxicants including Cd2+ both in vitro and in vivo. The mechanism of Zn2+-mediated protection from Cd2+-induced cytotoxicity is not established. In this study, we aimed to understand the effects of Zn2+ on Cd2+-induced cytotoxicity and apoptosis using PC12 cells. Cell viability and DNA fragmentation assays in PC12 cells exposed to Cd2+ and/or Zn2+ revealed that Cd2+ (5 and 10 μmol/L) alone induced significant cell death, and co-exposure to Zn2+ (5, 10, and 100 μmol/L) for 48 h had a protective effect. Assessment of intracellular free sulfhydryl levels and lactate dehydrogenase activity suggested that Cd2+ (10 μmol/L) induced oxidative stress and disrupted cell membrane integrity. Addition of Zn2+ (10 and 100 μmol/L) reduced Cd2+-mediated cytotoxicity. Changes in expression of the apoptotic factors Bax, Bcl-2, Bcl-x, and cytochrome c were measured via western blot and expression of caspase 9 was detected via reverse transcriptase polymerase chain reaction. Western blots showed that Zn2+ (10 and 100 μmol/L) suppressed Cd2+-induced apoptosis (10 μmol/L) by reducing cytochrome c release into the cytosol, and downregulating the proapoptotic protein, Bax. In addition, expression of caspase 9 was lower in Cd2+ (5 μmol/L)-treated PC12 cells when co-treated with Zn2+ (2 and 5 μmol/L). These findings suggest that the effective inhibition of Cd2+-induced apoptosis in PC12 cells by Zn2+ might be due to suppression of mitochondrial apoptosis pathway and inhibition of Cd2+-induced production of reactive oxygen species.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0009-2797
関連情報	PMID 28390674
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.cbi.2017.04.003