RGD Reference Report - Inhibition of phosphatidylcholine synthesis via the phosphatidylethanolamine methylation pathway impairs incorporation of bulk lipids into VLDL in cultured rat hepatocytes.

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Inhibition of phosphatidylcholine synthesis via the phosphatidylethanolamine methylation pathway impairs incorporation of bulk lipids into VLDL in cultured rat hepatocytes.
Authors:	Nishimaki-Mogami, T Yao, Z Fujimori, K
Citation:	Nishimaki-Mogami T, etal., J Lipid Res. 2002 Jul;43(7):1035-45.
RGD ID:	1626402
Pubmed:	PMID:12091487 (View Abstract at PubMed)
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 [(35)S]apolipoprotein (apo)B-48 from microsomal membranes into the lumen. However, bezafibrate treatment resulted in reduced VLDL-[(35)S]apoB-48 and increased [(35)S]apoB-48-containing particles in the HDL density range (HDL-[(35)S]apoB-48) within the lumen. Inhibition of PE methylation by bezafibrate or 3-deazaadenosine after the completion of HDL-[(35)S]apoB-48 assembly effectively decreased VLDL-[(35)S]apoB-48 secretion with a concomitant increase in HDL-[(35)S]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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Pemt	Rat	positive regulation of lipoprotein metabolic process		IMP			RGD

Cellular Component

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Apob	Rat	high-density lipoprotein particle		IDA			RGD
Apob	Rat	very-low-density lipoprotein particle		IDA			RGD
Apob	Rat	vesicle lumen		IDA			RGD

Objects Annotated

Genes (Rattus norvegicus)

Apob (apolipoprotein B)

Pemt (phosphatidylethanolamine N-methyltransferase)

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Inhibition of phosphatidylcholine synthesis via the phosphatidylethanolamine methylation pathway impairs incorporation of bulk lipids into VLDL in cultured rat hepatocytes.