Protein kinase C iota mediates lipid-induced apoptosis of human coronary artery endothelial cells

Abstract

Apoptosis is involved in the development and progression of atherosclerotic lesions. Protein kinase C (PKC) signalling is of importance in atherosclerosis as well as apoptosis. Therefore, we tested the involvement of PKC in lipid-induced apoptosis of human coronary artery endothelial cells (HCAEC). Protein expression of PKC isoforms α, βI, δ, ɛ, and ι was detected, whereas no relevant protein amounts of PKC isoforms βII, γ, η, θ, and ζ were found. Inhibition of classical and novel PKC isoforms by treatment with bisindolylmaleimide or PKC down-regulation by long-term treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA) could not prevent apoptosis induced by palmitate or stearate. In contrast, a specific myristoylated, cell-permeable PKC ζ/ι pseudosubstrate prevented lipid-induced apoptosis in HCAEC. Furthermore, saturated fatty acids activated PKC ι as evidenced by PKC ι down-regulation upon long-term treatment with stearate. Our data provide evidence that PKC ι is activated by saturated fatty acids and mediates lipid-induced apoptosis of HCAEC.