title: Phospholipase D1 modulates protein kinase C-epsilon in retinal pigment epithelium cells during inflammatory response.
abstract: Inflammation is a key factor in the pathogenesis of several retinal diseases. In view of the essential role of the retinal pigment epithelium in visual function, elucidating the molecular mechanisms elicited by inflammation in this tissue could provide new insights for the treatment of retinal diseases. The aim of the present work was to study protein kinase C signaling and its modulation by phospholipases D in ARPE-19 cells exposed to lipopolysaccharide. This bacterial endotoxin induced protein kinase C-α/βII phosphorylation and protein kinase-ε translocation to the plasma membrane in ARPE-19 cells. Pre-incubation with selective phospholipase D inhibitors demonstrated that protein kinase C-α phosphorylation depends on phospholipase D1 and 2 while protein kinase C-ε activation depends only on phospholipase D1. The inhibition of α and β protein kinase C isoforms with Go 6976 did not modify the reduced mitochondrial function induced by lipopolysaccharide. On the contrary, the inhibition of protein kinase C-α, β and ε with Ro 31-8220 potentiated the decrease in mitochondrial function. Moreover, inhibition of protein kinase C-ε reduced Bcl-2 expression and Akt activation and increased Caspase-3 cleavage in cells treated or not with lipopolysaccharide. Our results demonstrate that through protein kinase C-ε regulation, phospholipase D1 protects retinal pigment epithelium cells from lipopolysaccharide-induced damage.
authors: Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia (DBByF), Universidad Nacional del Sur (UNS), 8000 Bahía Blanca, Argentina.
authors: Paula E
authors: PE
authors: Tenconi
authors: Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia (DBByF), Universidad Nacional del Sur (UNS), 8000 Bahía Blanca, Argentina.
authors: Norma M
authors: NM
authors: Giusto
authors: Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia (DBByF), Universidad Nacional del Sur (UNS), 8000 Bahía Blanca, Argentina.
authors: Gabriela A
authors: GA
authors: Salvador
authors: Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 8000 Bahía Blanca, Argentina; Departamento de Biología, Bioquímica y Farmacia (DBByF), Universidad Nacional del Sur (UNS), 8000 Bahía Blanca, Argentina. Electronic address: mvmateos@criba.edu.ar.
authors: Melina V
authors: MV
authors: Mateos
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004075:Diglycerides; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D051744:Protein Kinase C-epsilon; D010739:Phospholipase D; C106801:phospholipase D1
keywords: Inflammation; Lipopolysaccharide (LPS); Phospholipase D (PLD); Protein kinase C (PKC); Retinal pigment epithelium (RPE)