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Minimal Ovarian Upregulation of Glutamate Cysteine Ligase Expression in Response to Suppression of Glutathione by Buthionine Sulfoximine



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  • Personal Author:
  • Description:
    The antioxidant tripeptide glutathione (GSH) protects ovarian follicles against oxidative damage that may lead to apoptotic death. The rate-limiting step in synthesis of GSH is catalyzed by glutamate cysteine ligase (GCL), a heterodimer composed of a catalytic subunit (GCLC), and a modifier subunit (GCLM). We hypothesized that GSH depletion in vivo or in vitro with buthionine sulfoximine (BSO), a specific inhibitor of GCL activity, would increase ovarian and granulosa cell GCL subunit expression. Ovarian glutathione levels are lowest on proestrous morning and increase to their highest levels on estrus and metestrus. Therefore, we treated rats on proestrous morning or on proestrous morning and again 12 h later to prevent the normal increase in ovarian glutathione between proestrus and estrus. Ovarian Gclc and Gclm mRNA levels and GCLC protein levels increased transiently by 1.4-1.5-fold at 8 h, but not at 12 or 24 h, after a single dose of BSO administered to adult rats on the morning of proestrus. GCLC protein levels were also modestly increased 1.4-fold at 12 h after a second dose of BSO. GCLM protein levels increased 1.4-fold at 24 h after a single dose of BSO, but not at other time points. BSO treatment did not significantly alter ovarian GCL enzymatic activity or the intraovarian localization of either GCL subunit mRNA. Treatment of a human granulosa cell line or primary rat granulosa cells with BSO suppressed intracellular GSH; however, there was no compensatory upregulation of GCL subunit protein or mRNA levels. These results demonstrate that ovarian follicles and granulosa cells are minimally able to respond to acute GSH depletion by upregulating expression of GCL. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0890-6238
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    186-196
  • Volume:
    21
  • Issue:
    2
  • NIOSHTIC Number:
    nn:20058437
  • Citation:
    Reprod Toxicol 2006 Feb; 21(2):186-196
  • Contact Point Address:
    Ulrike Luderer, Division of Occupational and Environmental Medicine, Department of Medicine, University of California at Irvine, 5201 California Avenue, Suite 100, Irvine, CA 92617, USA
  • Email:
    uluderer@uci.edu
  • CAS Registry Number:
    Glutathione (CAS RN 70-18-8)
  • Federal Fiscal Year:
    2006
  • Performing Organization:
    University of California Los Angeles
  • Peer Reviewed:
    True
  • Start Date:
    20050701
  • Source Full Name:
    Reproductive Toxicology
  • End Date:
    20270630
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:b8447403a56ade56ebd900157f0767b087632c83ba95912f2a2a7175ac38c87ea8fcc7a382c447043bdcb53e4510b80a01c91e251f8b767dd25d22ae362733dd
  • Download URL:
  • File Type:
    Filetype[PDF - 689.15 KB ]
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