Human glutathione S-transferases: radioimmunoassay studies on the expression of alpha-, mu- and pi-class isoenzymes in developing lung and kidney

Beckett, Geoffrey J.; Howie, A F; Hume, Robert; Matharoo, B.; Hiley, Christopher; Jones, Peter W.; Strange, Richard C.

doi:10.1016/0304-4165(90)90031-q

Cited by 42 publications

(19 citation statements)

References 17 publications

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“…GSTA1 and GSTA2 were detectable at low levels in these same cells. Beckett et al (1990) again corroborated these findings using radioimmunological analysis to show that GSTP1 expression decreased from 14.1 to 3.8 pmol/mg cytosol protein between the fetus and postnatal infants at 2 weeks to 2 years of age. GSTM decreased slightly (3.4 to 1.2 pmol/mg cytosol protein), but GSTA1 and GSTA2 remained relatively constant (1.0 and 0.3 pmol/mg cytosol protein, respectively).…”

Section: Glutathione S-transferasesupporting

confidence: 65%

“…In fetal tissue greater than 35 weeks of age, expression was restricted to collecting tubules and the distal loop of Henle. These data were corroborated by Beckett et al (1990) who demonstrated expression of GSTA1 and GSTA2 in 10 to 42 week fetal kidney at approximately 1.0 pmol/mg cytosol protein with an increase to 4.1 and 8.6 pmol/mg cytosol protein within the first 2 years of life, respectively. In contrast, GSTM decreased from 7.7 to 3.1 pmol/mg cytosol protein between the fetal and postnatal samples whereas GSTP1 levels remained constant (1.5 pmol/mg cytosol protein).…”

Section: Glutathione S-transferasesupporting

confidence: 58%

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The Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms: Table 1

McCarver¹,

Hines²

2002

J Pharmacol Exp Ther

323

151

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Changes in phase II drug-metabolizing enzyme expression during development, as well as the balance between phase I and phase II enzymes, can significantly alter the pharmacokinetics for a given drug or toxicant. Although our knowledge is incomplete, many of the phase II enzymes are expressed early in development. There is evidence for glutathione S-transferase A1/A2 (GSTA1/A2), GSTM, and GSTP1 in fetal liver, lung and kidney, although tissue-specific patterns and changes with time are observed. N-Acetyltransferase 1 (NAT1) activity also has been reported throughout gestation in fetal liver, adrenal glands, lung, kidney, and intestine. Only postnatal changes in NAT1 expression were apparent. Nothing is known about human NAT2 developmental expression. Some UDP-glucuronosyltransferase and sulfotransferase isoforms also are detectable in fetal liver and other tissues by the first or second trimester, and substantial changes in isoform expression patterns, as well as overall expression levels, are observed with increasing maturity. Finally, expression of both epoxide hydrolases 1 and 2 (EPHX1 and EPHX2) is observed in fetal liver, and for the former, increased expression with time has been documented. Less is known about ontogenic molecular control mechanisms. Limited data suggest that the hepatocyte nuclear factor and CCAAT/enhancer binding protein families are critical for fetal liver drug-metabolizing enzyme expression whereas D element binding protein and related factors may regulate postnatal hepatic expression. There is a paucity of data regarding mechanisms for the onset of extrahepatic fetal expression or specific mechanisms determining temporal switches, such as those observed within the CYP3A and flavin-containing monooxygenase families.Taking advantage of electrophilic functional groups already present on the molecule, or ones introduced during phase I metabolism, the phase II drug-metabolizing enzymes (DMEs) are characterized by their ability to conjugate xenobiotics using small molecular weight, organic donor molecules such as glutathione, UDP-glucuronic acid, or acetyl coenzyme A. These reactions generally result in pharmacological inactivation or detoxification, although instances of bioactivation are known. Conjugation products also can be substrates for specific transport enzymes, thus facilitating elimination from the body. Historically, research on DMEs has placed more emphasis on those catalyzing phase I versus phase II reactions. This also has been true with respect to studies on DME developmental expression. Given the importance of the conjugation enzymes in drug and toxicant disposition and, in particular, how the balance between phase I and phase II enzymes can dramatically alter pharmacokinetics and therefore therapeutic efficacy and/or xenobiotic toxicity, this area deserves increased attention.Advances in our understanding of phase II enzyme expression during ontogeny have been hampered by many of the same problems discussed for the phase I enzymes (Hines and McCarver, 2002). These ...

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Section: Glutathione S-transferasesupporting

confidence: 65%

Section: Glutathione S-transferasesupporting

confidence: 58%

The Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms: Table 1

McCarver¹,

Hines²

2002

J Pharmacol Exp Ther

323

151

View full text Add to dashboard Cite

show abstract

“…Their results suggested that GSTP1 is the most important GST isoform at these developmental stages, whereas expression of GSTA and GSTM1 is moderate and low, respectively. Their results are in line with those previously reported also indicating that GSTP1 is the most important GST enzyme during fetal development (Beckett et al, 1990). Normal development of the foregut in humans begins during the fourth week of embryonic life with the differentiation of the foregut endoderm into a ventral respiratory part and a dorsal esophageal part.…”

Section: Discussionsupporting

confidence: 93%

Evidence that polymorphic deletion of the glutathione S‐transferase gene, GSTM1, is associated with esophageal atresia

Filonzi

Magnani

Angelis

et al. 2010

Birth Defects Research

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Results suggest that the GSTM1(-/-) null genotype may play an important role in the development of EA during early embryogenesis as a consequence of altered detoxification processes both in children and in the mothers. We hypothesize that GSTM1 allelic loss could be responsible for reduced or null catalytic activity in tissues exposed to amniotic fluid, and inefficient detoxification could be a trigger altering proliferation/apoptotic pattern of gut-trachea separation.

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“…Expression of the P-class isoenzymes fell during in utero ontogeny in lung, the pattern of down-regulation being similar to that previously observed in liver. There was no change in the expression of this isoenzyme in kidney (Beckett et al, 1990).…”

Section: Phase II Enzymesmentioning

confidence: 61%

Role of biokinetics in risk assessment of drugs and chemicals in children

Zwart

Haenen

Versantvoort

et al. 2004

Regulatory Toxicology and Pharmacology

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Human glutathione S-transferases: radioimmunoassay studies on the expression of alpha-, mu- and pi-class isoenzymes in developing lung and kidney

Cited by 42 publications

References 17 publications

The Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms: Table 1

The Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms: Table 1

Evidence that polymorphic deletion of the glutathione S‐transferase gene, GSTM1, is associated with esophageal atresia

Role of biokinetics in risk assessment of drugs and chemicals in children

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