Inhibition of suicidal erythrocyte death by resveratrol

Aims: Pleiotropic effects of resveratrol include antioxidant activity and inhibition of cyclooxygenase with decrease of PGE(2) formation. In erythrocytes oxidation and PGE(2) activate Ca2+-permeable cation channels. The Ca2+-entry leads to activation of Ca2+-sensitive K+ channels with subsequent cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Cell shrinkage and phosphatidylserine exposure are hallmarks of suicidal erythrocyte death or eryptosis.Eryptotic cells adhere to the vascular wall thus compromising microcirculation and are cleared from circulating blood thus leading to anemia. The present experiments explored whether resveratrol influences eryptosis. Main methods: Erythrocyte phosphatidylserine exposure was identified by annexin V-binding, cell volume estimated from forward scatter and Cytosolic Ca2+ activity determined utilizing Fluo3 fluorescence in FACS analysis. Key findings: Energy depletion (48 h glucose removal) significantly increased FIuo(3) fluorescence and annexin V-binding and decreased forward scatter, effects significantly blunted by resveratrol (>= 5 mu M). Moreover, oxidative stress (30 min 0.3 mM tert-butylhydroperoxide) and isoosmotic cell shrinkage (48 h replacement of extracellular chloride by gluconate) similarly triggered eryptosis, effects again significantly blunted in the presence of resveratrol. Significance: Resveratrol is a potent inhibitor of suicidal erythrocyte death during energy depletion. oxidative stress and isoosmotic cell shrinkage. The nutrient could thus counteract anemia and impairment of microcirculation under conditions With excessive eryptosis. (C) 2009 Elsevier Inc. All rights reserved.