Hexavalent chromium-induced apoptosis of granulosa cells involves selective sub-cellular translocation of Bcl-2 members, ERK1/2 and p53

Journal Article · Tue Mar 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.01.011· OSTI ID:21535254

Stanley, Jone A; Lee, JeHoon; Stephen, Sam D; Arosh, Joe A ^[1]; Hoyer, Patricia B ^[2]; Burghardt, Robert C ^[1]

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1. Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A and M University, College Station, TX 77843 (United States)
2. Department of Physiology, University of Arizona, Tucson, AZ 85724-5051 (United States)

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 {mu}M 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.

• OSTI ID: 21535254
• Journal Information: Toxicology and Applied Pharmacology, Vol. 251, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.01.011; PII: S0041-008X(11)00020-2; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
ASCORBIC ACID
CATALYTIC CONVERTERS
CHROMIUM
DNA
HEALTH HAZARDS
HEAT-SHOCK PROTEINS
MITOCHONDRIA
OVARIES
PHOSPHORYLATION
RATS
ANIMALS
BODY
CELL CONSTITUENTS
CHEMICAL REACTIONS
ELEMENTS
EQUIPMENT
FEMALE GENITALS
GONADS
HAZARDS
MAMMALS
METALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POLLUTION CONTROL EQUIPMENT
PROTEINS
RODENTS
TRANSITION ELEMENTS
VERTEBRATES
VITAMINS