Monitoring Expression of Cytochrome P450 Genes During Postischemic Rat Liver Reperfusion Using DNA Microarrays

Takahashi, Yasuo; Nishida, Yusuke; Ishii, Yoshinori; Ito, Koichi; Asai, Satoshi

doi:10.1254/jphs.rc0040040

Cited by 5 publications

(3 citation statements)

References 9 publications

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“…Not many members of the CYP71D subfamily have been functionally characterized but the involvement of certain members in the biosynthesis of terpenoids has been reported before (Lupien et al, 1999;Takahashi et al, 2005). LjCYP71D353 represents a novel cytochrome P450 enzyme acting on an unusual triterpene skeletondihydrolupeolgiving rise via successive reactions to 20-hydroxy-lupeol and 20-hydroxybetulinic acid.…”

Section: Researchmentioning

confidence: 99%

A metabolic gene cluster in Lotus japonicus discloses novel enzyme functions and products in triterpene biosynthesis

et al. 2013

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SummaryGenes for triterpene biosynthetic pathways exist as metabolic gene clusters in oat and Arabidopsis thaliana plants. We characterized the presence of an analogous gene cluster in the model legume Lotus japonicus.In the genomic regions flanking the oxidosqualene cyclase AMY2 gene, genes for two different classes of cytochrome P450 and a gene predicted to encode a reductase were identified. Functional characterization of the cluster genes was pursued by heterologous expression in Nicotiana benthamiana. The gene expression pattern was studied under different developmental and environmental conditions. The physiological role of the gene cluster in nodulation and plant development was studied in knockdown experiments.A novel triterpene structure, dihydrolupeol, was produced by AMY2. A new plant cytochrome P450, CYP71D353, which catalyses the formation of 20-hydroxybetulinic acid in a sequential three-step oxidation of 20-hydroxylupeol was characterized. The genes within the cluster are highly co-expressed during root and nodule development, in hormone-treated plants and under various environmental stresses. A transcriptional gene silencing mechanism that appears to be involved in the regulation of the cluster genes was also revealed.A tightly co-regulated cluster of functionally related genes is involved in legume triterpene biosynthesis, with a possible role in plant development.

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Section: Researchmentioning

confidence: 99%

A metabolic gene cluster in Lotus japonicus discloses novel enzyme functions and products in triterpene biosynthesis

et al. 2013

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“…Using DNA microarray, Takahashi and colleagues [32] examined the hepatic expression of 50 CYP genes in Wistar-Kyoto rats that have been subjected to 15 min of ischemia and different periods of reperfusion. The authors showed a significant downregulation of eight CYP genes at 16 h after reperfusion, including CYP2C23, 2D3, 2J3, 3A18, 4A1, 4A10, and 4F4/27.…”

Section: Regulation Of Hepatic Drug Metabolism By Liver I/rmentioning

confidence: 99%

Regulation of drug-metabolizing enzymes by local and systemic liver injuries

Guo

Xie

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction Drug metabolism and disposition are critical in maintaining the chemical and functional homeostasis of xenobiotics/drugs and endobiotics. The liver plays an essential role in drug metabolism and disposition due to its abundant expression of drug-metabolizing enzymes (DMEs) and transporters. There is growing evidence to suggest that many hepatic and systemic diseases can affect drug metabolism and disposition by regulating the expression and/or activity of DMEs and transporters in the liver. Areas covered This review focuses on the recent progress on the regulation of DMEs by local and systemic liver injuries. Liver ischemia and reperfusion (I/R) and sepsis are used as examples of local and systemic injury, respectively. The reciprocal effect of the expression and activity of DMEs on animals' sensitivity to local and systemic liver injuries is also discussed. Expert opinion Local and systemic liver injuries have a major effect on the expression and activity of DMEs in the liver. Understanding the disease effect on DMEs is clinically important due to the concern of disease-drug interactions. Future studies are necessary to understand the mechanism by which liver injury regulates DMEs. Human studies are also urgently needed in order to determine whether the results in animals can be replicated in human patients.

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“…The effect of ischemic damage on liver metabolic enzyme activity has been reported by several investigators [8][9][10]. Izuishi et al [11] reported deterioration of liver drug-metabolizing enzyme activity lasting for up to 10 days after warm ischemia.…”

mentioning

confidence: 95%

Total body propofol clearance (TBPC) after living-donor liver transplantation (LDLT) surgery is decreased in patients with a long warm ischemic time

et al. 2006

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Metabolic capacity after liver transplant surgery may be affected by the graft size and by hepatic injury during the surgery. This study was carried out to investigate the postoperative total body propofol clearance (TBPC) in living-donor liver transplantation (LDLT) patients and to investigate the major factors that contribute to decreased postoperative TBPC in LDLT patients. Fourteen patients scheduled for LDLT were included in this study. Propofol was administered at a rate of 2.0 mg.kg(-1).h(-1) as a sedative in the intensive care unit (ICU) setting. To calculate TBPC, propofol arterial blood concentration was measured by HPLC. Five variables were selected as factors affecting postoperative TBPC; bleeding volume (BLD), warm ischemic time (WIT), cold ischemic time (CIT), graft weight/standard liver volume ratio (GW/SLV), and portal blood flow after surgery (PBF). After factor analysis of six variables, including TBPC, varimax rotation was carried out, and this yielded three interpretable factors that accounted for 75.5% of the total variance in the data set. TBPC, WIT, CIT, and BLD were loaded on the first factor, PBF on the second factor, and GW/SLV on the third factor. The adjusted correlation coefficient between TBPC and WIT showed the highest value (r = -0.61) in the first factor. The LDLT patients were divided into two groups according to WIT; group A (WIT > 100 min) and group B (WIT < 100 min). Mean TBPC values in group A and group B were 14.6 +/- 2.1 and 28.5 +/- 4.1 ml.kg(-1).min(-1), respectively (P < 0.0001). These data suggest that LDLT patients with a long WIT have a risk of deteriorated drug metabolism.

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Monitoring Expression of Cytochrome P450 Genes During Postischemic Rat Liver Reperfusion Using DNA Microarrays

Cited by 5 publications

References 9 publications

A metabolic gene cluster in Lotus japonicus discloses novel enzyme functions and products in triterpene biosynthesis

A metabolic gene cluster in Lotus japonicus discloses novel enzyme functions and products in triterpene biosynthesis

Regulation of drug-metabolizing enzymes by local and systemic liver injuries

Total body propofol clearance (TBPC) after living-donor liver transplantation (LDLT) surgery is decreased in patients with a long warm ischemic time

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