Phosphatidylinositol acts through mitogen-activated protein kinase to stimulate hepatic apolipoprotein A-I secretion
| Autor: | Nihar R. Pandey, Ayesha Misquith, Erin Twomey, Shawn Hopewell, Daniel L. Sparks |
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| Rok vydání: | 2008 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Apolipoprotein B medicine.drug_class Endocrinology Diabetes and Metabolism Gene Expression Phosphatidylinositols Models Biological chemistry.chemical_compound Endocrinology Internal medicine medicine Humans Secretion Phosphatidylinositol RNA Messenger Phosphorylation Protein kinase A Cells Cultured Phospholipase C biology Apolipoprotein A-I Kinase Protein kinase inhibitor Molecular biology Protein Transport chemistry Liver biology.protein lipids (amino acids peptides and proteins) Mitogen-Activated Protein Kinases Protein Processing Post-Translational Protein Binding |
| Zdroj: | Metabolism: clinical and experimental. 57(12) |
| ISSN: | 1532-8600 |
| Popis: | Phosphatidylinositol (PI) has been shown to stimulate reverse cholesterol transport in animal models and to increase plasma apolipoprotein (apo) A-I levels and high-density lipoprotein cholesterol in human subjects. The objective of this study was to determine the molecular mechanism through which PI stimulates apo A-I secretion in hepatic cells. PI (12 mumol/L) significantly stimulates apo A-I secretion from HepG2 cells over 24 hours. The stimulation in apo A-I secretion is completely blocked by phospholipase C inhibitors (D609 and U73122) and the Ras inhibitor sulindac sulfide. Apolipoprotein A-I secretion is augmented with a protein kinase C agonist (dioctanoyl glycerol) and inhibited by a protein kinase C inhibitor (dioleoyl ethylene glycol). The PI-induced apo A-I secretion is unaffected by PI-3-kinase inhibitors but is sensitive to mitogen-activated protein kinase (MAPK) inhibitors. Whereas the p38MAPK inhibitor SB203580 has no effect on PI-induced apo A-I secretion, the MAPK kinase 1/2 inhibitor U0126 and the c-Jun-N-terminal kinase/stress-activated protein kinase inhibitor SP600125 block PI-induced apo A-I secretion. PI also increased extracellular-regulated protein kinase 1 and 2 phosphorylation in HepG2 cells in a time-dependent manner. PI does not appear to stimulate apo A-I gene transcription, as cellular apo A-I messenger RNA levels remained unchanged over the 24-hour incubation. However, PI significantly decreases apo A-I binding and degradation in HepG2 cells. Collectively, the data suggest that PI acts through MAPK pathways to increase plasma apo A-I levels by protecting it from reuptake and degradation. |
| Databáze: | OpenAIRE |
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