Campus Units
Animal Science
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
4-15-2012
Journal or Book Title
Toxicology and Applied Pharmacology
Volume
260
Issue
2
First Page
201
Last Page
208
DOI
10.1016/j.taap.2012.02.014
Abstract
7,12-dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all developmental stages. This study investigated a role for the glutathione S-transferase (Gst) isoforms alpha (a), mu (m) and pi (p) and the transcription factors, Ahr and Nrf2, during DMBA-induced ovotoxicity, and their regulation by phosphatidylinositol-3 kinase (PI3K) signaling. Negative regulation of JNK by GSTP during DMBA exposure was also studied. Post-natal day (PND) 4 Fischer 344 rat ovaries were exposed to vehicle control (1% DMSO) ± DMBA (1 μM) or vehicle control (1% DMSO) ± LY294002 (PI3K inhibitor; 20 μM) for 1, 2, 4, or 6 days. Total RNA or protein was isolated, followed by RT-PCR or Western blotting to determine mRNA or protein level, respectively. Immunoprecipitation using an anti-GSTP antibody was performed to determine interaction between GSTP and JNK, followed by Western blotting to determine JNK and p-c-Jun protein level. DMBA had no impact on Gsta, Gstm or Nrf2 mRNA level, but increased Gstp mRNA and protein after 2 days. Ahr mRNA and protein increased after 2 and 4 days of DMBA exposure, respectively and DMBA increased NRF2 protein level after 4 days. JNK bound to GSTP was increased during DMBA exposure, with a concomitant decrease in unbound JNK and p-c-Jun. Ahr and Gstp mRNA were decreased (2 days) and increased (4 days) by PI3K inhibition, while Gstm mRNA increased (P < 0.05) after both time points, and there was no effect on Nrf2 mRNA. PI3K inhibition increased AHR, NRF2 and GSTP protein level. These findings support involvement of ovarian GSTP during DMBA exposure, and indicate a regulatory role for the PI3K signaling pathway on ovarian xenobiotic metabolism gene expression.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Copyright Owner
Elsevier Inc.
Copyright Date
2012
Language
en
File Format
application/pdf
Recommended Citation
Bhattacharya, Poulomi and Keating, Aileen F., "Protective role for ovarian glutathione S-transferase isoform pi during 7,12-dimethylbenz[a]anthracene-induced ovotoxicity" (2012). Animal Science Publications. 477.
https://lib.dr.iastate.edu/ans_pubs/477
Included in
Animal Experimentation and Research Commons, Animal Sciences Commons, Cell and Developmental Biology Commons, Genetics Commons, Molecular Genetics Commons
Comments
This is a manuscript of an article published as Bhattacharya, Poulomi, and Aileen F. Keating. "Protective role for ovarian glutathione S-transferase isoform pi during 7, 12-dimethylbenz [a] anthracene-induced ovotoxicity." Toxicology and applied pharmacology 260, no. 2 (2012): 201-208. doi: 10.1016/j.taap.2012.02.014. Posted with permission.