ArticleThe American journal of pathology2004
Mice deficient in glutathione transferase zeta/maleylacetoacetate isomerase exhibit a range of pathological changes and elevated expression of alpha, mu, and pi class glutathione transferases.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 67 citations in OpenAlex.
- LanCL2 Implicates in Testicular Redox Homeostasis and Acrosomal Maturation.Antioxidants (Basel, Switzerland) · 2024Article
- New Cases of Maleylacetoacetate Isomerase Deficiency with Detection by Newborn Screening and Natural History over 32 Years: Experience from a German Newborn Screening Center.International journal of neonatal screening · 2024Article
- Animal models of male subfertility targeted on LanCL1-regulated spermatogenic redox homeostasis.Lab animal · 2022Article
- Dental Pulp Stem Cell Heterogeneity: Finding Superior Quality "Needles" in a Dental Pulpal "Haystack" for Regenerative Medicine-Based Applications.Stem cells international · 2022Review
- Differential SOD2 and GSTZ1 profiles contribute to contrasting dental pulp stem cell susceptibilities to oxidative damage and premature senescence.Stem cell research & therapy · 2021Article
- Exposure of Rats to Multiple Oral Doses of Dichloroacetate Results in Upregulation of Hepatic Glutathione Transferases and NAD(P)H Dehydrogenase [Quinone] 1.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- GSTZ1-1 downregulates Wnt/β-catenin signalling in hepatocellular carcinoma cells.FEBS open bio · 2020Article
- GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Review
- GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.The EMBO journal · 2019Article
- GSTO1-1 plays a pro-inflammatory role in models of inflammation, colitis and obesity.Scientific reports · 2017Article
- Whole exome sequencing in the Framingham Heart Study identifies rare variation in HYAL2 that influences platelet aggregation.Thrombosis and haemostasis · 2017Article
- Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.Pharmacology & therapeutics · 2017Review
- GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate.Biochimica et biophysica acta · 2016Article
- The Genetic Architecture of Murine Glutathione Transferases.PloS one · 2016Article
- Mice lacking three Loci encoding 14 glutathione transferase genes: a novel tool for assigning function to the GSTP, GSTM, and GSTT families.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Targeting of two aspects of metabolism in breast cancer treatment.Cancer biology & therapy · 2014Article
- MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case-control study using a multilocus genotyping.Age (Dordrecht, Netherlands) · 2013Article
- RNA-sequencing quantification of hepatic ontogeny and tissue distribution of mRNAs of phase II enzymes in mice.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Proteomic analysis of glutathione S-transferase isoforms in mouse liver mitochondria.World journal of gastroenterology · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Glutathione transferase zeta (GSTZ1-1) is the major enzyme that catalyzes the metabolism of alpha-halo acids such as dichloroacetic acid, a carcinogenic contaminant of chlorinated water. GSTZ1-1 is identical with maleylacetoacetate isomerase, which catalyzes the penultimate step in the catabolic pathways for phenylalanine and tyrosine. In this study we have deleted the Gstz1 gene in BALB/c mice and characterized their phenotype. Gstz1(-/-) mice do not have demonstrable activity with maleylacetone and alpha-halo acid substrates, and other GSTs do not compensate for the loss of this enzyme. When fed a standard diet, the GSTZ1-1-deficient mice showed enlarged liver and kidneys as well as splenic atrophy. Light and electron microscopic examination revealed multifocal hepatitis and ultrastructural changes in the kidney. The addition of 3% (w/v) phenylalanine to the drinking water was lethal for young mice (<28 days old) and caused liver necrosis, macrovesicular steatosis, splenic atrophy, and a significant loss of circulating leukocytes in older surviving mice. GSTZ1-1-deficient mice showed constitutive induction of alpha, mu, and pi class GSTs as well as NAD(P)H:quinone oxidoreductase 1. The overall response is consistent with the chronic accumulation of a toxic metabolite(s). We detected the accumulation of succinylacetone in the serum of deficient mice but cannot exclude the possibility that maleylacetoacetate and maleylacetone may also accumulate.
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Registered trials
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