| Hexavalent chromium-induced apoptosis of granulosa cells involves selective sub-cellular translocation of Bcl-2 members, ERK1/2 and p53. | |
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MedLine Citation:
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PMID: 21262251 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 24h, with or without vitamin C pre-treatment for 24h. 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. |
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Authors:
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Sakhila K Banu; Jone A Stanley; Jehoon Lee; Sam D Stephen; Joe A Arosh; Patricia B Hoyer; Robert C Burghardt |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-01-22 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 251 ISSN: 1096-0333 ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-01 Completed Date: 2011-04-13 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 253-66 Citation Subset: IM |
Copyright Information:
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Published by Elsevier Inc. |
Affiliation:
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Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. skbanu@cvm.tamu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / pharmacology Apoptosis / drug effects* Ascorbic Acid / pharmacology* Chromium / toxicity* DNA Fragmentation / drug effects* Down-Regulation / drug effects Female Granulosa Cells / drug effects*, metabolism Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Proto-Oncogene Proteins c-bcl-2 / metabolism Rats Rats, Sprague-Dawley Tumor Suppressor Protein p53 / metabolism Up-Regulation / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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ES016605-01A2/ES/NIEHS NIH HHS; R03 ES016605-01A1/ES/NIEHS NIH HHS; R03 ES016605-02/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 18540-29-9/chromium hexavalent ion; 50-81-7/Ascorbic Acid; 7440-47-3/Chromium; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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