Immunohistochemical localization and activity of glutathione transferase zeta (GSTZ1-1) in rat tissues.
Glutathione transferase zeta (GSTZ1-1) catalyzes the biotransformation of a range of alpha-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.
Lantum
Hoffman B M
HB
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Baggs
Raymond B
RB
Krenitsky
Daria M
DM
Board
Philip G
PG
Anders
M W
MW
D000085:Acetates / Q000378:metabolism; D000096:Acetone / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D003999:Dichloroacetic Acid / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity; D005982:Glutathione Transferase / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008298:Maleates / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D013347:Subcellular Fractions
D000085:Acetates; D004785:Environmental Pollutants; D008298:Maleates; C460372:maleylacetone; D000096:Acetone; C120963:chlorofluoroacetic acid; D003999:Dichloroacetic Acid; C498692:Gstz1 protein, rat; D005982:Glutathione Transferase