Nicotine- and Tar-free Cigarette Smoke Extract Induces Cell Injury via Intracellular Ca2+-Dependent Subtype-Specific Protein Kinase C Activation

Nicotine- and tar-free cigarette smoke extract (CSE) is reported to induce cell damage via activation of protein kinase C (PKC) and NADPH oxidase (NOX) in rat C6 glioma cells. Here we determined PKC isozyme(s) activated by CSE and their activation mechanism. In C6 glioma cells, mRNAs for PKC alpha, PKC delta, PKC epsilon, and PKC iota were expressed. CSE triggered translocation of PKC alpha and PKC epsilon to plasma membrane. CSE-induced cell damage and PKC translocation were inhibited by chelating intracellular Ca2+ but not extracellular Ca2+. These results suggest that CSE induces cell damage through intracellular Ca2+-dependent activation of PKC alpha and PKC epsilon and subsequent NOX activation.