title: Palmitoyl lysophosphatidylcholine mediated mobilization of LPL to the coronary luminal surface requires PKC activation.
abstract: Following diazoxide (DZ) induced hypoinsulinemia, cardiac luminal lipoprotein lipase (LPL) increases [Cardiovasc. Res. 3 (2003) 788]. To identify circulating mediators that maintain high LPL in vivo, DZ hearts were perfused for 1 h in the presence or absence of glucose, triglyceride (TG), palmitic acid or palmitoyl lysophosphatidylcholine (PLPC). Only PLPC maintained high luminal LPL in DZ hearts, likely through enzyme recruitment from the cardiomyocyte. PLPC perfusion activated whole heart protein kinase C (PKC) epsilon. As calphostin pretreatment blocked PLPC induced PKC activation, and increases in luminal LPL activity, PKC activation is essential for the effects of PLPC. Incubation of myocytes with PLPC had no effects on either surface or intracellular LPL or PKC suggesting that PKC activation occurs in cells other than the myocyte or that metabolism of PLPC is required for its downstream effects. Since exposure of endothelial cells to PLPC activated PKC, whole heart PKC activation likely occurred in these cells. Incubation of myocytes with LPA, a phospholipase D (PLD) mediated breakdown metabolite of PLPC, significantly enhanced basal and heparin-releasable myocyte LPL activity, an effect that was duplicated by co-incubation of control myocytes with exogenous PLD and PLPC. Our data suggest that at least in the whole heart, the LPL augmenting property of PLPC likely requires endothelial PKC activation, formation of LPA, and mobilization of enzyme from the myocyte to the coronary lumen.
authors.affiliation: Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pulinilkunnil
authors.forename: Ding
authors.initials: D
authors.lastname: An
authors.forename: Patsy
authors.initials: P
authors.lastname: Yip
authors.forename: Nathan
authors.initials: N
authors.lastname: Chan
authors.forename: Dake
authors.initials: D
authors.lastname: Qi
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Ghosh
authors.forename: Ashraf
authors.initials: A
authors.lastname: Abrahani
authors.forename: Brian
authors.initials: B
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D010477:Perfusion; D010739:Phospholipase D / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D009281:Naphthalenes; D014280:Triglycerides; C061465:calphostin complex; C006065:We 201; D019308:Palmitic Acid; D006493:Heparin; D011493:Protein Kinase C; D008071:Lipoprotein Lipase; D010739:Phospholipase D; D005947:Glucose; D003981:Diazoxide; C032881:lysophosphatidic acid