| Autor: |
Rahman, Md. Mostafizur, Ukiana, Junki, Uson-Lopez, Rachael, Sikder, Md. Tajuddin, Saito, Takeshi, Kurasaki, Masaaki |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Chemico-Biological Interactions. 269:41-49 |
| ISSN: |
0009-2797 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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