Hexavalent chromium-induced apoptosis of granulosa cells involves selective sub-cellular translocation of Bcl-2 members, ERK1/2 and p53
| Autor: | Sakhila K. Banu, Joe A. Arosh, Robert C. Burghardt, Patricia B. Hoyer, Jone A. Stanley, Sam D. Stephen, JeHoon Lee |
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| Rok vydání: | 2011 |
| Předmět: |
Chromium
Programmed cell death Down-Regulation Apoptosis Bcl-xL Ascorbic Acid DNA Fragmentation Mitochondrion Toxicology Antioxidants Article Rats Sprague-Dawley Animals Mitogen-Activated Protein Kinase 1 Pharmacology Granulosa Cells Mitogen-Activated Protein Kinase 3 biology Cytochrome c Ascorbic acid Molecular biology Rats Up-Regulation Cytosol Proto-Oncogene Proteins c-bcl-2 biology.protein DNA fragmentation Female Tumor Suppressor Protein p53 |
| Zdroj: | Toxicology and Applied Pharmacology. 251:253-266 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2011.01.011 |
| Popis: | Hexavalent chromium (CrVI) has been widely used in industries throughout the world. Increased usage of CrVI and atmospheric emission of CrVI from catalytic converters of automobiles, and its improper disposal causes various health hazards including female infertility. Recently we have reported that lactational exposure to CrVI induced a delay/arrest in follicular development at the secondary follicular stage. In order to investigate the underlying mechanism, primary cultures of rat granulosa cells were treated with 10 μM potassium dichromate (CrVI) for 12 and 24 h, with or without vitamin C pre-treatment for 24 h. The effects of CrVI on intrinsic apoptotic pathway(s) were investigated. Our data indicated that CrVI: (i) induced DNA fragmentation and increased apoptosis, (ii) increased cytochrome c release from the mitochondria to cytosol, (iii) downregulated anti-apoptotic Bcl-2, Bcl-XL, HSP70 and HSP90; upregulated pro-apoptotic BAX and BAD, (iv) altered translocation of Bcl-2, Bcl-XL, BAX, BAD, HSP70 and HSP90 to the mitochondria, (v) upregulated p-ERK and p-JNK, and selectively translocated p-ERK to the mitochondria and nucleus, (vi) activated caspase-3 and PARP, and (vii) increased phosphorylation of p53 at ser-6, ser-9, ser-15, ser-20, ser-37, ser-46 and ser-392, increased p53 transcriptional activation, and downregulated MDM-2. Vitamin C pre-treatment mitigated CrVI effects on apoptosis and related pathways. Our study, for the first time provides a clear insight into the effect of CrVI on multiple pathways that lead to apoptosis of granulosa cells which could be mitigated by vitamin C. |
| Databáze: | OpenAIRE |
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