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Research ArticleArticle

Immunohistochemical Localization and Activity of Glutathione Transferase Zeta (GSTZ1–1) in Rat Tissues

Hoffman B. M. Lantum, Raymond B. Baggs, Daria M. Krenitsky, Philip G. Board and M. W. Anders
Drug Metabolism and Disposition June 2002, 30 (6) 616-625; DOI: https://doi.org/10.1124/dmd.30.6.616
Hoffman B. M. Lantum
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Raymond B. Baggs
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Daria M. Krenitsky
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Philip G. Board
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M. W. Anders
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Abstract

Glutathione transferase zeta (GSTZ1–1) catalyzes the biotransformation of a range of α-haloacids, including dichloroacetic acid (DCA), and the penultimate step in the tyrosine degradation pathway. DCA is a rodent carcinogen and a common drinking water contaminant. DCA also causes multiorgan toxicity in rodents and dogs. The objective of this study was to determine the expression and activities of GSTZ1–1 in rat tissues with maleylacetone and chlorofluoroacetic acid as substrates. GSTZ1–1 protein was detected in most tissues by immunoblot analysis after immunoprecipitation of GSTZ1–1 and by immunohistochemical analysis; intense staining was observed in the liver, testis, and prostate; moderate staining was observed in the brain, heart, pancreatic islets, adrenal medulla, and the epithelial lining of the gastrointestinal tract, airways, and bladder; and sparse staining was observed in the renal juxtaglomerular regions, skeletal muscle, and peripheral nerve tissue. These patterns of expression corresponded to GSTZ1–1 activities in the different tissues with maleylacetone and chlorofluoroacetic acid as substrates. Specific activities ranged from 258 ± 17 (liver) to 1.1 ± 0.4 (muscle) nmol/min/mg of protein with maleylacetone as substrate and from 4.6 ± 0.89 (liver) to 0.09 ± 0.01 (kidney) nmol/min/mg of protein with chlorofluoroacetic acid as substrate. Rats given DCA had reduced amounts of immunoreactive GSTZ1–1 protein and activities of GSTZ1–1 in most tissues, especially in the liver. These findings indicate that the DCA-induced inactivation of GSTZ1–1 in different tissues may result in multiorgan disorders that may be associated with perturbed tyrosine metabolism.

Footnotes

  • This research was supported in part by the University of Rochester Wilmot Cancer Research Fellowship Program (H.B.M.L.) and by National Institute of Environmental Health Sciences Grant ES03127 (M.W.A.).

  • Abbreviations used are::
    GST
    glutathione transferases
    GSTZ
    glutathione transferase zeta
    DCA
    dichloroacetic acid
    CFA
    chlorofluoroacetic acid
    MA
    maleylacetone
    GSTA
    glutathione transferase alpha
    GSTM
    glutathione transferase mu
    GSTP
    glutathione transferase pi
    GSTT
    glutathione transferase theta
    GSTO
    glutathione transferase omega
    FA
    fumarylacetone
    CHAPS
    3-[(3-cholamidopropyl)dimethylammonio]-propanesulfonate
    • Received November 5, 2001.
    • Accepted February 21, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 30 (6)
Drug Metabolism and Disposition
Vol. 30, Issue 6
1 Jun 2002
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Research ArticleArticle

Immunohistochemical Localization and Activity of Glutathione Transferase Zeta (GSTZ1–1) in Rat Tissues

Hoffman B. M. Lantum, Raymond B. Baggs, Daria M. Krenitsky, Philip G. Board and M. W. Anders
Drug Metabolism and Disposition June 1, 2002, 30 (6) 616-625; DOI: https://doi.org/10.1124/dmd.30.6.616

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Research ArticleArticle

Immunohistochemical Localization and Activity of Glutathione Transferase Zeta (GSTZ1–1) in Rat Tissues

Hoffman B. M. Lantum, Raymond B. Baggs, Daria M. Krenitsky, Philip G. Board and M. W. Anders
Drug Metabolism and Disposition June 1, 2002, 30 (6) 616-625; DOI: https://doi.org/10.1124/dmd.30.6.616
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