Intracellular Ca²⁺ is an essential factor for cell damage induced by unsaturated carbonyl compounds

The unsaturated carbonyl compounds are known as the environmental pollutants. Acrolein (ACR) and methyl vinyl ketone (MVK) are representative unsaturated carbonyl compounds. ACR is contained in smoke, automobile exhaust, industrial waste, and several foods. MVK is widely used as the industrial chemical. Although ACR and MVK are highly toxic, the molecular mechanism for their cytotoxicity has been unclear. We have previously reported that ACR and MVK are major cytotoxic compounds in the gas phase of cigarette smoke, and protein kinase C (PKC) inhibitor and NADPH oxidases inhibitor partially rescued cells from ACR- or MVK-induced cell death (Noya et al., Toxicology, 314, 1-10, 2013). PKC translocation, which is hallmark for PKC activation, and cell damage were induced by treatment of cultured cells with ACR or MVK. Intracellular Ca²⁺ chelator completely suppressed ACR- or MVK-induced PKC translocation to the cell membrane and cell damage, while extracellular Ca²⁺ chelator had no effects on ACR- and MVK-induced cytotoxicity. These results suggest that intracellular Ca²⁺ is an essential factor for cell damage caused by both PKC-dependent and PKC-independent pathways, and mobilization of Ca²⁺ from intracellular Ca²⁺ stores is induced by ACR or MVK.