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

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Title: Cytotoxic effects of cadmium and zinc co-exposure in PC12 cells and the underlying mechanism
Authors: Rahman, Md. Mostafizur Browse this author
Ukiana, Junki Browse this author
Uson-Lopez, Rachael Browse this author
Sikder, Md. Tajuddin Browse this author
Saito, Takeshi Browse this author →KAKEN DB
Kurasaki, Masaaki Browse this author →KAKEN DB
Keywords: apoptosis
heavy metals
cytochrome c
caspase 9
Issue Date: 2-Apr-2018
Journal Title: Chemico-Biological Interactions
Volume: 269
Start Page: 41
End Page: 49
Publisher DOI: 10.1016/j.cbi.2017.04.003
PMID: 28390674
Abstract: 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.
Rights: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:環境科学院・地球環境科学研究院 (Graduate School of Environmental Science / Faculty of Environmental Earth Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 藏崎 正明

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