TY - JOUR
T1 - Immunohistochemical localization and activity of glutathione transferase zeta (GSTZ1-1) in rat tissues
AU - Lantum, Hoffman B.M.
AU - Baggs, Raymond B.
AU - Krenitsky, Daria M.
AU - Board, Philip G.
AU - Anders, M. W.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036265997&partnerID=8YFLogxK
U2 - 10.1124/dmd.30.6.616
DO - 10.1124/dmd.30.6.616
M3 - Article
SN - 0090-9556
VL - 30
SP - 616
EP - 625
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 6
ER -