Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces

被引:60
作者
van Helvoort, A
de Brouwer, A
Ottenhoff, R
Brouwers, JFHM
Wijnholds, J
Beijnen, JH
Rijneveld, A
van der Poll, T
van der Valk, MA
Majoor, D
Voorhout, W
Wirtz, KWA
Elferink, RPJO
Borst, P
机构
[1] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands
[2] Netherlands Canc Inst, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands
[3] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands
[4] Netherlands Canc Inst, Div Pathol, NL-1066 CX Amsterdam, Netherlands
[5] Univ Amsterdam, Acad Med Ctr, Dept Gastrointestinal & Liver Dis, NL-1105 AZ Amsterdam, Netherlands
[6] Univ Amsterdam, Acad Med Ctr, Lab Expt Internal Med, NL-1105 AZ Amsterdam, Netherlands
[7] Univ Utrecht, Dept Lipid Biochem, Ctr Biomembranes & Lipid Enzymol, NL-3584 CH Utrecht, Netherlands
[8] Slotervaart Hosp, Dept Pharm, NL-1066 EC Amsterdam, Netherlands
[9] Univ Utrecht, Grad Sch Anim Hlth, Dept Biochem & Cell Biol, NL-3584 CM Utrecht, Netherlands
关键词
D O I
10.1073/pnas.96.20.11501
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Phosphatidylcholine transfer protein (Pc-tp) is a highly specific carrier of phosphatidylcholine (PC) without known function. Proposed functions include the supply of PC required for secretion into bile or lung air space (surfactant) and the facilitation of enzymatic reactions involving PC synthesis or breakdown. To test these functions, we generated knock-out mice unable to make Pc-tp, Remarkably these mice are normal and have no defect in any of the postulated Pc-tp functions analyzed. The lipid content and composition of the bile, as well as lung surfactant secretion and composition, of Pc-tp (-/-) mice, is normal, The lack of a Pc-tp contribution to biliary lipid secretion is in agreement with our finding that Pc-tp is down-regulated in adult mouse liver: whereas Pc-tp is abundant in the liver of mouse pups, Pc-tp levels decrease > 10-fold around 2 wk after birth, when bile formation starts. In adult mice, Pc-tp levels are high only in epididymis, testis, kidney, and bone marrow-derived mast cells. Absence of Pc-tp in bone marrow-derived mast cells does not affect their lipid composition or PC synthesis and degradation. We discuss how PC might reach the canalicular membrane of the hepatocyte for secretion into the bile, if not by Pc-tp.
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页码:11501 / 11506
页数:6
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