The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDLs⃞
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 e...
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| Format: | Article |
| Language: | English |
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Elsevier
2009-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520414683 |
| _version_ | 1824024962455830528 |
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| author | Maroun Bou Khalil Meenakshi Sundaram Hong-Yu Zhang Philip H. Links Jennifer F. Raven Boripont Manmontri Meltem Sariahmetoglu Khai Tran Karen Reue David N. Brindley Zemin Yao |
| author_facet | Maroun Bou Khalil Meenakshi Sundaram Hong-Yu Zhang Philip H. Links Jennifer F. Raven Boripont Manmontri Meltem Sariahmetoglu Khai Tran Karen Reue David N. Brindley Zemin Yao |
| author_sort | Maroun Bou Khalil |
| collection | DOAJ |
| description | 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 (Sf > 100) and VLDL2 (Sf 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. |
| first_indexed | 2024-12-19T09:54:50Z |
| format | Article |
| id | doaj.art-c7e2e3e0875044f584544925221558a8 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T09:54:50Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-c7e2e3e0875044f584544925221558a82022-12-21T20:26:51ZengElsevierJournal of Lipid Research0022-22752009-01-015014758The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDLs⃞Maroun Bou Khalil0Meenakshi Sundaram1Hong-Yu Zhang2Philip H. Links3Jennifer F. Raven4Boripont Manmontri5Meltem Sariahmetoglu6Khai Tran7Karen Reue8David N. Brindley9Zemin Yao10Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Departments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Phosphatidate 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 (Sf > 100) and VLDL2 (Sf 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.http://www.sciencedirect.com/science/article/pii/S0022227520414683fatty liver dystrophyhepatosteatosistriacylglycerolhypertriglyceridemiadiabetesdexamethasone |
| spellingShingle | Maroun Bou Khalil Meenakshi Sundaram Hong-Yu Zhang Philip H. Links Jennifer F. Raven Boripont Manmontri Meltem Sariahmetoglu Khai Tran Karen Reue David N. Brindley Zemin Yao The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDLs⃞ Journal of Lipid Research fatty liver dystrophy hepatosteatosis triacylglycerol hypertriglyceridemia diabetes dexamethasone |
| title | The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDLs⃞ |
| title_full | The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDLs⃞ |
| title_fullStr | The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDLs⃞ |
| title_full_unstemmed | The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDLs⃞ |
| title_short | The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDLs⃞ |
| title_sort | level and compartmentalization of phosphatidate phosphatase 1 lipin 1 control the assembly and secretion of hepatic vldls⃞ |
| topic | fatty liver dystrophy hepatosteatosis triacylglycerol hypertriglyceridemia diabetes dexamethasone |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520414683 |
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