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标题：The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDL
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作者：Maroun Bou Khalil ; Meenakshi Sundaram ; Hong-Yu Zhang 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：2009
卷号：50
期号：1
页码：47-58
DOI：10.1194/jlr.M800204-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Phosphatidate phosphatase-1 (PAP-1) converts phosphatidate to diacylglycerol and plays a key role in the biosynthesis of phospholipids and triacylglycerol (TAG). PAP-1 activity is encoded by members of the lipin family, including lipin-1 (1α and 1β), -2, and -3. We determined the effect of lipin-1 expression on the assembly and secretion of very low density lipoproteins (VLDL) using McA-RH7777 cells. Expression of lipin-1α or -1β increased the synthesis and secretion of [³H]glycerol-labeled lipids under either basal- or oleate-supplemented conditions. In the presence of oleate, the increased TAG secretion was mainly associated with VLDL₁ ( S_f > 100) and VLDL₂ ( S_f 20–100). Expression of lipin-1α or -1β increased secretion efficiency and decreased intracellular degradation of [³⁵S]apolipoprotein B-100 (apoB100). Knockdown of lipin-1 using specific short interfering RNA decreased secretion of [³H]glycerolipids and [³⁵S]apoB100 even though total PAP-1 activity was not decreased, owing to the presence of lipin-2 and -3 in the cells. Deletion of the nuclear localization signal sequences within lipin-1α not only abolished nuclear localization but also resulted in impaired association with microsomal membranes. Cells expressing the cytosolic lipin-1α mutant failed to promote [³⁵S]apoB100 synthesis or secretion, and showed compromised stimulation in [³H]TAG synthesis and secretion. Thus, alteration in hepatic expression of lipin-1 and its compartmentalization control VLDL assembly/secretion.