Biliary components are transported by hepatic @entity855 -binding cassette (ABC) transporters that are located in canalicular membranes. Physiological transporter function is related to membrane fluidity, which is modulated by the phospholipid composition of the lipid bilayer. We hypothesized that @entity1448 may alter transporter function by modifying phospholipid species to protect the cell from cholestatic damage. Therefore, we examined the expression of ABC transport proteins and their mRNA levels in canalicular membrane vesicles isolated from @entity35 liver 6 hr or three days after bile duct ligation. Membrane lipid composition and membrane fluidity of both sinusoidal and canalicular membrane vesicles were also examined. By 6 hr after bile duct ligation, we found a clear increase of @entity32224 and @entity30167 mRNA. These changes were associated with an increase of mdr- @entity22209 and with a clear decrease of @entity21998 protein, and small decrease of @entity30167 protein. In addition, mdrlb mRNA showed a strong increase by three days after bile duct ligation. Canalicular membrane fluidity decreased in a marked time-dependent manner, whereas sinusoidal membranes showed biphasic changes: increased fluidity at 6 hr and a decrease at three days. These changes were closely related to the changes of membrane lipid constitution; the saturated/ @entity5031 ratio increased for @entity2434 in canalicular membrane and the reverse occurred in sinusoidal membrane, and those for @entity4291 showed the opposite pattern. We conclude that @entity1448 causes modulation of ABC transporters as well as that of the lipid constitution in lipid bilayer. These may confer cytoprotective resistance to hepatocytes against cholestatic stress.

Phospholipid alterations in hepatocyte membranes and transporter protein changes in cholestatic XXXX model.

@entity30167 :: ('83569(Tax:10116)', 'Gene') :: ['bsep'] @entity4291 :: ('CHEBI:17636', 'Chemical') :: ['sphingomyelin'] @entity32224 :: ('24891(Tax:10116)', 'Gene') :: ['mdr2'] @entity2434 :: ('MESH:D010713', 'Chemical') :: ['phosphatidylcholine'] @entity21998 :: ('25303(Tax:10116)', 'Gene') :: ['mrp2'] @entity1448 :: ('MESH:D002779', 'Disease') :: ['cholestasis'] @entity5031 :: ('CHEBI:27208', 'Chemical') :: ['unsaturated fatty acid'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity22209 :: ('287115(Tax:10116)', 'Gene') :: ['Pgp'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['adenosine triphosphate']
@entity35 :: (10116,Species) :: ['rat']
