Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha (HNF1α)-deficient mice

Cheung, Connie; Akiyama, Taro E.; Kudo, Gen; Gonzalez, Frank J.

doi:10.1016/s0006-2952(03)00586-0

Cited by 74 publications

(65 citation statements)

References 57 publications

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“…They have demonstrated that in pig, binding of two transcription factors (HNF-1 and COUP-TF1) to CYP2E1 could activate the promoter. The regulation of the expression of hepatic CYP2E1 by HNF-1 has previously been shown in mice [7] but the activation of the CYP2E1 promoter by COUP-TF1 is a novel observation, which may be specific to the pig species. In man, targeted disruption of the HNF-1α gene leads to a decreased expression of CYP2E1 [28].…”

Section: Phase I Metabolismmentioning

confidence: 88%

Genetic and metabolic aspects of androstenone and skatole deposition in pig adipose tissue: A review(Open Access publication)

Robic

Larzul²,

Bonneau³

2007

Genet. Sel. Evol.

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-High levels of androstenone and skatole in fat tissues are considered the primary causes of boar taint, an unpleasant odour and flavour of the meat from non-castrated male pigs. The aim of this article is to review our current knowledge of the biology and genetic control of the accumulation of androstenone and skatole in fat tissue. Two QTL mapping studies have shown the complexity of the genetic control of these traits. During the last ten years, several authors have taken a more physiological approach to investigate the involvement of genes controlling the metabolism of androstenone and skatole. Although some authors have claimed the identification of candidate genes, it is more appropriate to talk about target genes. This suggests that genes affecting androstenone and skatole levels will have to be sought for among specific or non-specific transcription factors interacting with these target genes.androstenone / skatole / pig / boar taint / QTL

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Section: Phase I Metabolismmentioning

confidence: 88%

Genetic and metabolic aspects of androstenone and skatole deposition in pig adipose tissue: A review(Open Access publication)

Robic

Larzul²,

Bonneau³

2007

Genet. Sel. Evol.

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“…The mechanism of the unique regulation of Cyp2a5 during these conditions is unclear and remains to be investigated. The one demonstrated mechanism that is common in these conditions is, in part, oxidative stress (Kirby et al, 1994b;Chomarat et al, 1997;Nebert et al, 2000;Cheung et al, 2003;Gilmore et al, 2003;Gilmore and Kirby, 2004;Su and Ding, 2004;Weng et al, 2005;Chen and Siddiqui, 2007;Fisher et al, 2009;De-Oliveira et al, 2010). Furthermore, these conditions appear to be associated with increased serum bilirubin levels (Bonacini, 2004;Malaguarnera et al, 2005;Richardson et al, 2006b;Hansen, 2010).…”

Section: Pathophysiological States Associated With Cyp2a5mentioning

confidence: 99%

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Kim

Antenos

Squires

et al. 2013

Toxicology and Applied Pharmacology

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Murine cytochrome P450 2A5 (CYP2A5) is an interesting enzyme for its unique regulation and its involvement in liver injury caused by various well-known pathological conditions or hepatotoxins. It has been reported that CYP2A5 is upregulated following exposure to chemical hepatotoxins and during pathophysiological conditions in which the levels of most Cytochrome P450s are either unchanged or down-regulated. Recently bilirubin has been identified as the first endogenous substrate for CYP2A5 and it has been suggested that CYP2A5 plays a major role in bilirubin clearance as an alternative mechanism to BR conjugation by UGT1A1. This study investigated the mechanisms of gene regulation and cytoprotective role of CYP2A5 in response to bilirubin treatment in liver. Our results demonstrate that bilirubin induces CYP2A5 expression at the mRNA and protein levels by increasing CYP2A5 transcription via a mechanism that involves Nrf2 activation. Furthermore, our results suggest that induced CYP2A5 plays a cytoprotective role against bilirubin toxicity by directly lowering the cellular levels of bilirubin and by inhibiting caspase-3 activation.iii ACKNOWLEDGEMENTS

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“…1 A, B), and hence translational control (Graves et al, 1995;Monfar et al, 1995;Harris and Lawrence, 2003). The glucagon, cyclic nucleotide activated PKA signaling cascade is also complex and appears to involve activation of LKB1 and AMP kinase (AMPK), which phosphorylates other targets, including HNF1α, the transcription factor reported for regulating CYP2E1 gene transcription (Cheung et al, 2003), and HNF4α ( Fig. 1 A,B).…”

Section: Overview Of Glucagon Cyclic Nucleotides Pka Ampk Signalingmentioning

confidence: 99%

The role of intracellular signaling in insulin-mediated regulation of drug metabolizing enzyme gene and protein expression

Kim

Novak

2007

Pharmacology & Therapeutics

143

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Endogenous factors, including hormones, growth factors and cytokines, play an important role in the regulation of hepatic drug metabolizing enzyme expression in both physiological and pathophysiological conditions. Alterations of hepatic drug metabolizing enzymes gene and protein expression, observed in diabetes, fasting, obesity, protein-calorie malnutrition and long-term alcohol consumption alters the metabolism of xenobiotics, including procarcinogens, carcinogens, toxicants, and therapeutic agents and may also impact the efficacy and safety of therapeutic agents, as well as result in drug-drug interactions. Although the mechanisms by which xenobiotics regulate drug metabolizing enzymes have been studied intensively, less is known regarding the cellular signaling pathways and components which regulate drug metabolizing enzyme gene and protein expression in response to hormones and cytokines. Recent findings, however, have revealed that several cellular signaling pathways are involved in hormone-and growth factor-mediated regulation of drug metabolizing enzymes. Our laboratory, and others, have demonstrated that insulin and growth factors regulate drug metabolizing enzyme gene and protein expression, including cytochromes P450, glutathione S-transferases and microsomal epoxide hydrolase, through receptors which are members of the large receptor tyrosine kinase family, and by downstream effectors such as phosphatidylinositol 3-kinase, the mitogen activated protein kinase, Akt/protein kinase B, mTOR, and the p70S6 kinase. Here, we review current knowledge of the signaling pathways implicated in regulation of drug metabolizing enzyme gene and protein expression in response to insulin and growth factors, with the goal of increasing our understanding of how chronic disease affects these signaling pathways, components, and ultimately gene expression and translational control.

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Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha (HNF1α)-deficient mice

Cited by 74 publications

References 57 publications

Genetic and metabolic aspects of androstenone and skatole deposition in pig adipose tissue: A review(Open Access publication)

Genetic and metabolic aspects of androstenone and skatole deposition in pig adipose tissue: A review(Open Access publication)

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

The role of intracellular signaling in insulin-mediated regulation of drug metabolizing enzyme gene and protein expression

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