We are analyzing https://link.springer.com/article/10.1007/s00204-012-0902-7.

Title:
A dual function of the furanocoumarin chalepensin in inhibiting Cyp2a and inducing Cyp2b in mice: the protein stabilization and receptor-mediated activation | Archives of Toxicology
Description:
Chalepensin, a furanocoumarin, is present in several medicinal Rutaceae plants and causes a mechanism-based inhibition of human and mouse cytochrome P450 (P450, CYP) 2A in vitro. To address the in vivo effect, we investigated the effects of chalepensin on multiple hepatic P450 enzymes in C57BL/6JNarl mice. Oral administration of 10 mg/kg chalepensin to mice for 7 days significantly decreased hepatic coumarin 7-hydroxylation (Cyp2a) and increased 7-pentoxyresorufin O-dealkylation (Cyp2b) activities, whereas activities of Cyp1a, Cyp2c, Cyp2e1, and Cyp3a were not affected. Without affecting its mRNA level, the decreased Cyp2a activity was accompanied by an increase in the immunodetected Cyp2a5 protein level. In chalepensin-treated mice, microsomal Cyp2a5 was less susceptible to ATP-fortified cytosolic degradation than that in control mice, resulting in the elevated protein level. The in vitro inactivation through NADPH-fortified pre-incubation with chalepensin also protected microsomal Cyp2a5 against protein degradation. Using cell-based reporter systems, chalepensin at a concentration near unbound plasma concentration activated mouse constitutive androstane receptor (CAR), in agreement with the observed induction of Cyp2b. These findings revealed that suicidal inhibition of Cyp2a5 and the CAR-mediated Cyp2b9/10 induction concurrently occurred in chalepensin-treated mice.
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Keywords {🔍}

article, google, scholar, cas, pubmed, cypa, cytochrome, mice, receptor, chalepensin, human, cypb, protein, ueng, hepatic, pharmacol, university, chen, liver, toxicol, biochem, chem, national, taipei, taiwan, content, research, lim, souček, yunefang, mechanismbased, inhibition, access, institute, roc, privacy, cookies, induction, pregnane, characterization, biol, medical, function, information, publish, search, toxicology, yunping, yun, mouse,

Topics {✒️}

high-resolution gas-chromatographic analysis chul-ho yun constitutive androstane receptor month download article/chapter yune-fang ueng nadph-fortified pre-incubation differential inductive profiles nuclear receptors sxr/pxr sánchez-monterrubio pnhernández-bautista carbon monoxide-binding pigment hepatic triphosphopyridine nucleotide-cytochrome chih-chien hsu miss yu-ping chang yun-ping lim atp-fortified cytosolic degradation selective mechanism-based inactivator drug-metabolizing enzyme systems hepatic drug-metabolizing enzymes phenobarbital pretreated dba/2j nnk-induced lung tumorigenesis mouse cytochrome p450 national yang-ming university cell-based reporter systems increased 7-pentoxyresorufin o-dealkylation liver coumarin 7-hydroxylases single-dose methoxsalen effects human liver microsomes full article pdf chien-chih chen cytochrome p450 enzymes receptor-mediated activation author information authors cytochrome p450 2a6 decreased cyp2a activity cytochrome p450 ubiquitination female c57bl/6jnarl mice privacy choices/manage cookies national research institute hepatic cytochrome p450s guengerich fp elevated protein level human cytochromes p450 mechanism-based inhibition steroid receptor coactivator-1 check access instant access cytochrome p4502 c9 related subjects microsomal subcellular fractions article lo

Questions {❓}

Correia MA, Sadeghi S, Mundo-Paredes E (2005) Cytochrome P450 ubiquitination: branding for the proteolytic slaughter?
Faouzi S, Medzihradszky KF, Hefner C, Maher JJ, Correia MA (2007) Characterization of the physiological turnover of native and inactivated cytochrome P450 3A in cultured rat hepatocytes: a role for the cytosolic AAA ATPase p97?

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