Propylthiouracil inducible glutathione transferases

Lee, Eibai; Okuno, Shiroh; Kariya, Kimio

doi:10.1016/0006-2952(86)90300-x

Cited by 17 publications

(4 citation statements)

References 24 publications

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“…Interestingly, phenobarbital appears to induce the synthesis of GST both in periportal and pericentral cells, despite the fact that in the basal state the amount of GST within hepatocytes appears to be greatest in pericentral cells (77,78). The increase in GST activity following administration of propylthiouracil also appears to be due largely to an increase in the YaYa form of GST (79). The increase in specific isozymes is due to increases in levels of mRNA.…”

Section: Expression and Inductionmentioning

confidence: 99%

Special article the glutathione S-transferases: An update

Boyer

1989

Hepatology

208

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Over the last 15 years, we have passed through an initial period in which multiple forms of GST in various organs and different species were identified and characterized. The focus of current research is to define the role of the numerous isozymes in cell function, to ascertain the relationship between structure and function of different isozymes and to determine how the expression of GST is regulated in different tissues. During these studies, it is expected that new roles for the GST will be proposed, and this family of multifunctional proteins will continue to hold the interest of numerous investigators for many years.

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Section: Expression and Inductionmentioning

confidence: 99%

Special article the glutathione S-transferases: An update

Boyer

1989

Hepatology

208

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“…Rat tissues contain at least 18 dimers made up of 13 different subunits (Mannervik & Danielson, 1988;Ketterer et al, 1988;Kispert et al, 1989;Hayes et al, 1990a,b;Hiratsuka et al, 1990;Meyer et al, 1991). GST activity is regulated at the transcriptional level by a variety of inducing compounds, including phenobarbital (Pickett et al, 1984;Ding et al, 1986;Di Simplicio et al, 1989), 3-methylcholanthrene (Pickett et al, 1984;Rushmore et al, 1990), propylthiouracil (Lee et al, 1986) and antioxidants (Di Simplicio et al, 1989;Benson et al, 1989). GST isoenzyme profiles are also altered in carcinogenesis and multi-drug-resistance, often with an appearance of Pi class GST (Satoh et al, 1985;Cowan et al, 1986;Moscow et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Tissue distribution of enzymic methylation of glutathione S-transferase and its effects on catalytic activity. Methylation of glutathione S-transferase 11-11 inhibits conjugating activity towards 1-chloro-2,4-dinitrobenzene

Johnson

Finn

Siegel

1992

Biochemical Journal

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Glutathione S-transferases (GSTs) were isolated from rat liver, lung, heart, kidney, testis and brain by coupled affinity chromatography and subunits were resolved by reverse-phase h.p.l.c. The reverse-phase h.p.l.c. technique was improved from our previously published work [Johnson, Neal, Collins & Siegel (1990) Biochem. J. 270, 483-489] by changing from a C4 to a C18 wide-pore reverse-phase column; this resulted in baseline or near-baseline resolution of all GST subunits. There were significant tissue-dependent differences in the expression of GST subunits and the level of GST subunits present was quantitatively determined for each of the tissues. The extent of methylation of GSTs in vitro and distribution of GST methyltransferase (GST-MT) was determined in cytosolic fractions from each of these tissues. Purified GST isoenzymes were methylated with partially purified liver GST-MT. Methylation of Mu class subunits 3 and 4, the preferred substrates of methylation in liver, was substoichiometric in all tissues. The extent of methylation of subunit 3 ranged from 0.13% to 0.94% and subunit 4 from 0.03% to 0.60%. Methylation of Alpha class subunits was either not detectable or 5-10-fold less than that of Mu class subunits 3 and 4. Pi class subunit 7 was methylated to a greater extent than the Alpha class subunits but less than Mu class isoenzymes. A notable exception to this low level of methylation was GST 11-11, found mainly in testis and brain. Methylation of subunit 11 reached 21.9% (219 pmol of methyl group/nmol of subunit 11) when this isoenzyme was incubated with partially purified liver GST methyltransferase. Methylation of GST 11-11 was found to inhibit the conjugating activity of this isoenzyme towards 1-chloro-2,4-dinitrobenzene; the degree of inhibition of conjugating activity correlated with the extent of methylation of GST 11-11. GST-MT activity toward GST subunits 3, 4 and 11 was present in kidney and liver, detectable in lung and heart, but absent from brain and testis. Anion-exchange chromatography of GST-MTs from liver and kidney suggested the presence of four different forms of GST-MT (I-IV) and indicated that GST-MT isoenzymes III and IV were present at significantly lower concentrations in kidney than liver. The present paper shows that methylation is an enzyme-catalysed reaction that differs in substrate-specificity with respect to different GST isoenzymes, that expression of GST-MT is tissue-dependent and multiple forms of the enzyme are present in liver and kidney, and that methylation inhibits GST activity.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Cytosolic GST isoenzyme profiles are altered in preneoplastic foci, tumor tissue, and multidrug-resistant cell lines (Satoh et al, 1985;Cowan et al, 1986;Moscow et al, 1989). Enzymatic activity is regulated at the transcriptional level by a variety of inducing compounds (Pickett et al, 1984;Ding et al, 1986;Lee et al, 1986;Benson et al, 1989;Di Simplicio et al, 1989;Rushmore et al, 1990). In contrast, no compounds have been shown to increase hepatic concentrations of microsomal GST (Morgenstem and DePierre, 1985;McLellan and Hayes, 1989;McLellan et al, 199 1).…”

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confidence: 99%

Glutathione S-transferase isoenzymes in rat brain neurons and glia

et al. 1993

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The glutathione S-transferases (GSTs) constitute a family of cytosolic isoenzymes and a structurally unrelated microsomal enzyme that is involved in the detoxication of electrophilic xenobiotics. These enzymes also participate in the intracellular binding and transport of a broad range of lipophilic compounds including bilirubin, and hormones such as the glucocorticoids and thyroid hormones. The present investigation demonstrates that GSTs are present in neurons of the brainstem, forebrain, and cerebellum. An isoenzyme-specific distribution of GSTs was found in cytoplasm, nuclei, and nucleoli. The regional and cellular distribution of cytosolic GSTs in the brain was studied by immunohistochemistry, spectrophotometric enzyme assay, and reverse-phase HPLC. Polyclonal antibody against microsomal GST was strongly reactive with Purkinje cells throughout the cerebellar cortex, and with neurons in the brainstem and hippocampus. Nuclei of Purkinje cells and of neurons in the brainstem, hippocampus, and cerebral cortex were immunopositive for alpha-class GST 1-1 (YaYa), whereas alpha-class GST 2-2 (YcYc) antibody was consistently immunoreactive with the nucleolus, but not with the nucleus or soma. All alpha-class GST antibodies studied were reactive, to various degrees, with astrocytes and choroid plexus; however, ependymal cells of the subventricular zones were immunonegative. alpha-class GST 8-8 (YkYk) immunoreactivity was specifically localized to endothelial cells and/or astrocytic end feet associated with blood vessels. Reverse-phase HPLC indicated that there were also substantial regional differences in the pattern of alpha-, mu-, and pi-class GST subunit expression. For example, the thalamus/hypothalamus had the highest GST activity and greatest concentration of total GST protein and mu-class GST subunit 6 (Yb3), whereas the brainstem had the greatest concentration of pi-class GST subunit (Yp). This regional variation in GST expression may be reflective of regional differences in cell populations. In cerebellar cortex, the concentration of mu-class GST subunit 4 (Yb2) was greatest in the flocculus and lowest in the vermis. This is of clinical interest because the pattern of expression of mu-class GST subunit 4 (Yb2) in the cerebellum coincides with the known regional susceptibility of this structure to degeneration after exposure to toxic or metabolic insults. The vermis is most susceptible to these insults, whereas the lateral lobes and flocculus are most resistant.(ABSTRACT TRUNCATED AT 400 WORDS)

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Propylthiouracil inducible glutathione transferases

Cited by 17 publications

References 24 publications

Special article the glutathione S-transferases: An update

Special article the glutathione S-transferases: An update

Tissue distribution of enzymic methylation of glutathione S-transferase and its effects on catalytic activity. Methylation of glutathione S-transferase 11-11 inhibits conjugating activity towards 1-chloro-2,4-dinitrobenzene

Glutathione S-transferase isoenzymes in rat brain neurons and glia

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