Ascorbate protects endothelial barrier function during septic insult: Role of protein phosphatase type 2A

摘要: Endothelial barrier dysfunction contributes to morbidity in sepsis. We tested the hypothesis that raising intracellular ascorbate concentration protects endothelial from septic insult by inhibiting protein phosphatase type 2A. Monolayer cultures of microvascular cells were incubated with ascorbate, dehydroascorbic acid (DHAA), NADPH oxidase inhibitors apocynin and diphenyliodonium, or PP2A inhibitor okadaic then exposed (lipopolysaccharide interferon-γ). Under standard culture conditions depleted stimulated oxidant production activity, dephosphorylated phosphoserine phosphothreonine residues tight junction-associated occludin, decreased abundance occludin at cell borders, increased monolayer permeability albumin. prevented activation leak, showing these changes required reactive oxygen species. Okadaic acid, a inhibited activity dephosphorylation redistribution, implicating response insult. Incubation DHAA raised concentrations mitigated effects In conclusion, acts within inhibit stimulation thereby prevents activation, PP2A-dependent redistribution disruption barrier.