|Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
This study was undertaken to clarify factors that regulate intraheaptic lipid molecules trafficking and its clinical implications. Using intra- and extra-hepatic cholestatic model, changes in lipid composition and fluidity of liver plasma membranes as well as ABC transporter expression. Cholestasis caused a biphasic changes in canalicular membrane fluidity ; an increase at 6 hr and a decrease at 3 days. Further, a reciprocal change in canalicular and sinusoidal membrane composition and function was evident under cholestasis, suggesting the compensatory relationship between those. In contrast, ABC transporter expression was not altered drastically, although the biliary secretion of bile constituents was reduced. Thus, it is deduced that cholestasis modulates the lipid molecular composition at plasma membrane bilayers to affect their fluidity., and that this alters function of ABC transporters without drastic changes in their expression. The compensatory changes found between sinusoidal and canalicular membrane composition and function suggests that the regulation of intrahepatic lipid molecule trafficking plays a role in the hepatocellular physiology, and therefore, the factor affecting this trafficking is very likely to be an important target for clinical strategy to chronic liver diseases ; i. e., viral hepatitis, intrahepatic cholestasis such as PBC and PSC.