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

Abstract

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 PKCα, PKCδ, PKCε, and PKCι were expressed. CSE triggered translocation of PKCα and PKCε 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 PKCα and PKCε and subsequent NOX activation.