Protein kinase C-dependent cell damage by unsaturated carbonyl compounds in vascular cells

Unsaturated carbonyl compounds, such as acrolein (ACR) and methyl vinyl ketone (MVK), are known as the environmental pollutants, and are contained in smoke, automobile exhaust, and heated oil. Although they can enter the circulation through the alveolar epithelium, the details of their effects on the vascular system remain to be clarified. We have recently reported that ACR and MVK induce protein kinase C (PKC) activation and cell damage mediated by intracellular Ca2+ in rat glioma cells (Higashi et al., J. Biosci. Bioeng., 124, 680–684, 2017). In this study, we have attempted to elucidate the effects of ACR and MVK on the vascular system, because blood vessels are easily exposed to these compounds. The rat aorta smooth muscle cells A7r5 were highly sensitive to ACR and MVK, whereas the human umbilical vein endothelial cells EA.hy926 were resistant to them. The ACR- and MVK-induced cell damage in A7r5 cells was PKC-dependent. In A7r5 cells, PKCα, PKCδ, PKCe, and PKCι were expressed. ACR and MVK induced PKCα and PKCδ translocation to the cell membrane. PKC activity was enhanced in A7r5 cells by ACR and MVK. These results indicate that the unsaturated carbonyl compounds might affect the vascular system by damaging smooth muscle cells via PKC activation.