PLD1-PKCε pathway protects from LPS-induced cell damage in retinal pigment epithelium cells

SALVADOR, G.A.; GIUSTO, N.M.; TENCONI, P.E.; MATEOS, M.V.

Córdoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

SAIB

Inflammation is a key factor in the pathogenesis of several retinal diseases. In view of the essential role of the retinal pigment epithelium (RPE) 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 (PKC) signaling and its modulation by phospholipases D (PLD) in ARPE-19 RPE cells exposed to lipopolysaccharide (LPS). Western blot, immunocytochemistry and confocal microscopy assays showed that LPS induces activation of PKCα and ε. The pre-incubation with selective PLD inhibitors (EVJ and APV) demonstrated that PKCα activation depends on both classical PLDs (PLD1 and PLD2) while PKCε activation depends only on PLD1. The inhibition of PKCα and β with Go6976 did not modify the reduced cell viability induced by LPS. On the contrary, the inhibition of PKCα, β and ε with Ro31-8220 potentiated the decrease in cell viability triggered by LPS, suggesting that PKCε mediates cell survival. Moreover, inhibition of PKCε reduced Bcl-2 expression and Akt activation and increased cleaved Caspase-3, both in cells treated or not with LPS. Our results demonstrate that PLD1 through PKCε regulation protects RPE from LPS-induced damage.