|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,6ß,7ß,12
-tetrahydroxy-5ß-cholan-24-oic acid in spgp knockout mice







* Department of Pharmacology, Universitè de Montréal, Montréal, Canada H3C 3J7
Centre de Recherche de l'Hôpital Sainte-Justine, Montréal, Canada H3T 1C5
British Columbia Cancer Research Center, BC Cancer Agency, Vancouver, BC, Canada V5Z 1L3
** The Hospital for Sick Children, Department of Pathology, University of Toronto, Toronto, ON, Canada M5G 1X8
1 To whom correspondence should be addressed. e-mail: ibrahim.yousef{at}umontreal.ca
Bile formation and its canalicular secretion are essential functions of the mammalian liver. The sister-of-p-glycoprotein (spgp) gene was shown to encode the canalicular bile salt export protein, and mutations in spgp gene were identified as the cause of progressive familial intrahepatic cholestasis type 2. However, target inactivation of spgp gene in mice results in nonprogressive but persistent cholestasis and causes the secretion of unexpectedly large amounts of unknown tetrahydroxylated bile acid in the bile. The present study confirms the identity of this tetrahydroxylated bile acid as 3
,6ß,7ß,12
-tetrahydroxy-5ß-cholan-24-oic acid. The data further show that in serum, liver, and urine of the spgp knockout mice, there is a significant increase in the concentration of total bile salts containing a large amount of tetrahydroxy-5ß-cholan-24-oic acid. The increase in total bile acids was associated with up-regulation of the mRNA of cholesterol 7
-hydroxylase in male mice only.
It is suggested that the lower severity of the cholestasis in the spgp knockout mice may be due to the synthesis of 3
,6ß,7ß,12
-tetrahydroxy-5ß-cholan-24-oic acid, which neutralizes in part the toxic effect of bile acids accumulated in the liver.
Supplementary key words bile salt cholestasis canalicular membrane knockout mice gas chromatography mass spectrometry electrospray tandem mass spectrometry sister-of-p-glycoprotein
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
H.-U. Marschall, M. Wagner, K. Bodin, G. Zollner, P. Fickert, J. Gumhold, D. Silbert, A. Fuchsbichler, J. Sjovall, and M. Trauner Fxr-/- mice adapt to biliary obstruction by enhanced phase I detoxification and renal elimination of bile acids J. Lipid Res., March 1, 2006; 47(3): 582 - 592. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |