The nuclear hormone receptor CAR (Constitutive Androstane Receptor) is a key regulator of the metabolism of a wide range of xenobiotic compounds. This proposal is focused on a newly identified role of CAR in the bilirubin metabolism pathway. Preliminary results demonstrate that CAR is a key regulator of bilirubin clearance pathway in mice. The overall goals of this project are to extend this finding to human CAR and begin to explore its role in neonatal jaundice as well as its role in mediating a well-known Chinese medicine in the treatment of jaundice.
The specific aims of this proposal are: 1) Determine the role of human CAR in regulation of bilirubin metabolism. 2) Compare the level of expression of CAR in human neonatal livers with adult livers. 3) Determine the role of CAR in mediating the effect of a Chinese medicine, Yinzhi Huang, in treatment of human jaundice. The findings will elucidate the essential role of CAR in bilirubin metabolism and have significant implications for development of more potent drugs for the treatment of human jaundice and other related diseases.
| Blanco-Bose, William E; Murphy, Mark J; Ehninger, Armin et al. (2008) C-Myc and its target FoxM1 are critical downstream effectors of constitutive androstane receptor (CAR) mediated direct liver hyperplasia. Hepatology 48:1302-11 |
| Baskin-Bey, Edwina S; Huang, Wendong; Ishimura, Norihisa et al. (2006) Constitutive androstane receptor (CAR) ligand, TCPOBOP, attenuates Fas-induced murine liver injury by altering Bcl-2 proteins. Hepatology 44:252-62 |
| Zhang, Jun; Huang, Wendong; Qatanani, Mohammed et al. (2004) The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J Biol Chem 279:49517-22 |
