文章基本信息

标题：Inhibition of phosphatidylcholine synthesis via the phosphatidylethanolamine methylation pathway impairs incorporation of bulk lipids into VLDL in cultured rat hepatocytes
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作者：Tomoko Nishimaki-Mogami ; Zemin Yao ; Kannosuke Fujimori 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2002
卷号：43
期号：7
页码：1035-1045
DOI：10.1194/jlr.M100354-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Inhibition of phosphatidylcholine (PC) synthesis via the phosphatidylethanolamine (PE) methylation pathway was shown to decrease the secretion of VLDL from primary rat hepatocytes (Nishimaki-Mogami et al. 1996. Biochim. Biophys. Acta. 1304: 21–31). To understand further the role of PE methylation, we determined the effect of bezafibrate, an inhibitor of PE methylation, on VLDL assembly within the microsomal lumen. Bezafibrate was shown to decrease VLDL (triacylglycerol) secretion only when cellular PE methylation was active in the presence of methionine. Pulse-chase experiments showed that bezafibrate treatment did not impair the movement of [³⁵S]apolipoprotein (apo)B-48 from microsomal membranes into the lumen. However, bezafibrate treatment resulted in reduced VLDL-[³⁵S]apoB-48 and increased [³⁵S]apoB-48-containing particles in the HDL density range (HDL-[³⁵S]apoB-48) within the lumen. Inhibition of PE methylation by bezafibrate or 3-deazaadenosine after the completion of HDL-[³⁵S]apoB-48 assembly effectively decreased VLDL-[³⁵S]apoB-48 secretion with a concomitant increase in HDL-[³⁵S]apoB-48 secretion. These findings suggest that inhibition of PC synthesis via the PE methylation pathway impairs the stage of bulk triacylglycerol incorporation during the assembly of VLDL.