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Article
Dual protective role for Glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary
Toxicology and Applied Pharmacology
  • Aileen F. Keating, Iowa State University
  • Nivedita Sen, University of Arizona
  • I. Glenn Sipes, University of Arizona
  • Patricia B. Hoyer, University of Arizona
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
9-1-2010
DOI
10.1016/j.taap.2010.06.002
Abstract

The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S-transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extraovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80mg/ Kg/d; 15d, i.p). The present study investigated the pattern of ovarian GSTp expression during VCD exposure. Additionally, the effect of VCD on an ovarian GSTp:JNK protein complex was investigated. PND4 F344 rat ovaries were incubated in control medium ± VCD (30 μM) for 2-8d. VCD increased ovarian GSTp mRNA (P <0.05) relative to control on d4-d8; whereas GSTp protein was increased (P < 0.05) on d6-d8. A GSTp:JNK protein complex was detected by immunoprecipitation and Western blotting in ovarian tissues. Relative to control, the amount of GSTp-bound JNK was increased (P = 0.09), while unbound JNK was decreased (P < 0.05) on d6 of VCD exposure. The VCD-induced decrease in unbound JNK was preceded by a decrease in phosphorylated c-Jun which occurred on d4. These findings are in support of a possible dual protective role for GSTp in the rat ovary, consisting of metabolism of VCD and inhibition of JNKinitiated apoptosis.

Comments

This is a manuscript of an article published as Keating, Aileen F., Nivedita Sen, I. Glenn Sipes, and Patricia B. Hoyer. "Dual protective role for glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary." Toxicology and applied pharmacology 247, no. 2 (2010): 71-75.10.1016/j.taap.2010.06.002. Posted with permission.

Creative Commons License
Creative Commons Attribution-Noncommercial-No Derivative Works 4.0
Copyright Owner
Elsevier Inc.
Language
en
File Format
application/pdf
Citation Information
Aileen F. Keating, Nivedita Sen, I. Glenn Sipes and Patricia B. Hoyer. "Dual protective role for Glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary" Toxicology and Applied Pharmacology Vol. 247 Iss. 2 (2010) p. 71 - 75
Available at: http://works.bepress.com/aileen-keating/30/