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Hokkaido University Collection of Scholarly and Academic Papers >
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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 | | DNA | | caspase 9 | | glutathione |
| 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/68652 |
| 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)
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Submitter: 藏崎 正明
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