Title |
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Cytotoxic effects of cadmium and zinc co-exposure in PC12cells and the underlying mechanism
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Creator |
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Rahman, Md. Mostafizur
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Accessrights |
open access |
Rights |
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© 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/
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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
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Subject |
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Other
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apoptosis
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heavy metals
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cytochrome c
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DNA
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caspase 9
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Other
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glutathione
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NDC
450
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Description |
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Abstract
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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.
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Date |
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Language |
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Resource Type |
journal article |
Version Type |
AM |
Identifier |
HDL
http://hdl.handle.net/2115/68652
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Relation |
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isVersionOf
DOI
https://doi.org/10.1016/j.cbi.2017.04.003
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PMID
28390674
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Journal |
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Chemico-Biological Interactions
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Volume Number269
Page Start41
Page End49
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File |
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Oaidate |
2023-07-26 |