3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase (Tiparp) Knockout Mice

Cho, Tiffany E.; Bott, Debbie; Ahmed, Shaimaa; Hutin, David; Gomez, Alvaro; Tamblyn, Laura; Zhou, Angela; Watts, Tania H.; Grant, Denis M.; Matthews, Jason

doi:10.3390/ijms20092312

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…The association between PARP10 and PCNA helps cells bypass stalls at replication forks and resume DNA synthesis. PARP7, however, has not been directly linked to DNA repair but does function in transcription regulation, cellular autophagy, immunity, and response to viral infections [12]. This review will focus primarily on PARP1 and PARP2 as most inhibitors act upon these enzymes.…”

Section: Parp Family Of Enzymesmentioning

confidence: 99%

The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review

et al. 2020

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Poly(ADP-ribose) polymerase (PARP) inhibitors represent one of the successful novel approaches to targeted cancer treatment. Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these agents, certain challenges remain with their use. Among the most important are primary and secondary resistance. Here, we review the mechanism of action of PARP inhibitors and their ability to exploit certain inherent deficiencies among malignant cells to improve cell killing, with a focus on deficiencies in homologous recombination among cells with BRCA1 and BRCA2 mutations. Moreover, we discuss the different mechanisms of resistance including development of secondary resistance and strategies to overcome them. Finally, we discuss the limitations of novel therapeutic interventions and possible future studies to exploit biochemical pathways in order to improve therapeutic efficacy of PARP inhibitors.

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Section: Parp Family Of Enzymesmentioning

confidence: 99%

The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review

et al. 2020

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“…CYP1A1, CYP1B1 and TIPARP are the target genes of AHR [ 46 , 47 ]. The mRNA levels of these target genes are significantly enhanced by I3P and I3A, which are inhibited by CH223191, a specific AHR inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Human Chorionic Gonadotropin-Stimulated Interleukin-4-Induced-1 (IL4I1) Promotes Human Decidualization via Aryl Hydrocarbon Receptor

Luo

Zhang

et al. 2023

IJMS

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Decidualization is necessary for the successful establishment of early pregnancy in rodents and humans. Disturbed decidualization results in recurrent implantation failure, recurrent spontaneous abortion, and preeclampsia. Tryptophan (Trp), one of the essential amino acids in humans, has a positive effect on mammalian pregnancy. Interleukin 4-induced gene 1 (IL4I1) is a recently identified enzyme that can metabolize L-Trp to activate aryl hydrocarbon receptor (AHR). Although IDO1-catalyzed kynurenine (Kyn) from Trp has been shown to enhance human in vitro decidualization via activating AHR, whether IL4I1-catalyzed metabolites of Trp are involved in human decidualization is still unknown. In our study, human chorionic gonadotropin stimulates IL4I1 expression and secretion from human endometrial epithelial cells through ornithine decarboxylase-induced putrescine production. Either IL4I1-catalyzed indole-3-pyruvic acid (I3P) or its metabolite indole-3-aldehyde (I3A) from Trp is able to induce human in vitro decidualization by activating AHR. As a target gene of AHR, Epiregulin induced by I3P and I3A promotes human in vitro decidualization. Our study indicates that IL4I1-catalyzed metabolites from Trp can enhance human in vitro decidualization through AHR-Epiregulin pathway.

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“…Tiparp −/− and Tiparp Hep −/− mice exhibit increased AHR activity and increased sensitivity to TCDD-induced toxicities and wasting syndrome ( Ahmed et al , 2015 ; Hutin et al , 2018 ). This increased sensitivity to AHR ligands is not limited to TCDD, since 3-methylcholanthrene treatment also causes severe toxicity and lethality to Tiparp −/− mice ( Cho et al , 2019 ). Overall, the TCDD-treated Tiparp H532A mice exhibited many, if not all, of the same phenotypes as similarly treated Tiparp −/− and Tiparp Hep −/− mice.…”

Section: Discussionmentioning

confidence: 99%

2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)-Inducible Poly-ADP-Ribose Polymerase (TIPARP/PARP7) Catalytic Mutant Mice (TiparpH532A) Exhibit Increased Sensitivity to TCDD-Induced Hepatotoxicity and Lethality

Hutin

Long

Sugamori

et al. 2021

Toxicological Sciences

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP/PARP7), an aryl hydrocarbon receptor (AHR) target gene and mono-ADP-ribosyltransferase, acts as part of a negative feedback loop to repress AHR signaling. This process is prevented by a single H532A mutation in TIPARP that destroys its catalytic activity. We hypothesized that the loss of TIPARP catalytic activity would increase sensitivity to TCDD-induced toxicity in vivo. To test this, we created a catalytically deficient mouse line (TiparpH532A ) by introducing a single H532A mutation in TIPARP. Treatment of mouse embryonic fibroblasts or hepatocytes isolated from TiparpH532A mice confirmed the increased TCDD-induced expression of the AHR target genes Cyp1a1, Cyp1b1 and Tiparp. TiparpH532A mice given a single injection of 10 µg/kg TCDD, a non-lethal dose in Tiparp+/+ mice, did not survive beyond day 10. All Tiparp+/+ mice survived the 30-day treatment. TCDD-treated TiparpH532A mice displayed increased expression of AHR target genes, increased steatohepatitis and hepatotoxicity. Hepatic RNA-sequencing revealed 7-fold more differentially expressed genes (DEGs) in TiparpH532A mice than in Tiparp+/+ mice (4542 vs 647 genes) 6 days after TCDD treatment. DEGs included genes involved in xenobiotic metabolism, lipid homeostasis and inflammation. Taken together, these data further support TIPARP as a critical negative regulator of AHR activity and show that loss of its catalytic activity is sufficient to increase sensitivity to TCDD-induced steatohepatitis and lethality. Since TIPARP inhibition has recently emerged as a potential anti-cancer therapy, the impact on AHR signaling and aromatic hydrocarbon toxicity will need to be carefully considered under conditions of therapeutic TIPARP inhibition.

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3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase (Tiparp) Knockout Mice

Cited by 7 publications

References 36 publications

The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review

The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review

Human Chorionic Gonadotropin-Stimulated Interleukin-4-Induced-1 (IL4I1) Promotes Human Decidualization via Aryl Hydrocarbon Receptor

2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)-Inducible Poly-ADP-Ribose Polymerase (TIPARP/PARP7) Catalytic Mutant Mice (TiparpH532A) Exhibit Increased Sensitivity to TCDD-Induced Hepatotoxicity and Lethality

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