TCPOBOP is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss[1]. TCPOBOP attenuates Fas-induced murine liver injury by alteringBcl-2 proteins[2].
Constitutive androstane receptor (CAR) belonging to the nuclear receptor superfamily plays an important role in the xenobiotic metabolism and disposition[1]. TCPOBOP is a mCAR agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss (EC50 = 20 nM). TCPOBOP-induced direct hyperplasia has been considered to be CAR-dependent with no evidence of involvement of cytokines or growth factor signaling[2]. Expression of CYP2B10 and CYP3A11, known CAR target genes, increased 30-fold and 45-fold, respectively, in TCPOBOP-treated mice fed the MCD diet. TCPOBOP treatment reduced hepatic steatosis (44.6 +/- 5.4% vs 30.4 +/- 4.5%, P < 0.05) and serum triglyceride levels (48 +/- 8 vs 20 +/- 1 mg/dL, P < 0.05) in MCD diet-fed mice as compared with the standard diet-fed mice. This reduction in hepatic steatosis was accompanied by an increase in enzymes involved in fatty acid microsomal omega-oxidation and peroxisomal beta-oxidation, namely CYP4A10, LPBE, and 3-ketoacyl-CoA thiolase. The reduction in steatosis was also accompanied by a reduction in liver cell apoptosis and inflammation[3]. Hepatocyte proliferation induced by TCPOBOP was associated with a stronger proliferative response and earlier S phase entry in c-jun(Δli) mice, compared to WT animals.[4].
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