title: 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 Ca(2+) but not extracellular Ca(2+). These results suggest that CSE induces cell damage through intracellular Ca(2+)-dependent activation of PKCα and PKCε and subsequent NOX activation.
authors.affiliation: Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Mai
authors.forename: Tsunehito
authors.initials: T
authors.lastname: Higashi
authors.forename: Koji
authors.initials: K
authors.lastname: Terada
authors.forename: Chizuru
authors.initials: C
authors.lastname: Hatate
authors.forename: Prabha
authors.initials: P
authors.lastname: Nepal
authors.forename: Mika
authors.initials: M
authors.lastname: Horiguchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Harada
authors.forename: Soichi
authors.initials: S
authors.lastname: Miwa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horinouchi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D005910:Glioma / Q000201:enzymology* / Q000473:pathology*; D019255:NADPH Oxidases / Q000378:metabolism; D009538:Nicotine / Q000009:adverse effects*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species; D012906:Smoke / Q000009:adverse effects*; D013638:Tars; D062789:Tobacco Products / Q000009:adverse effects*; D014407:Tumor Cells, Cultured
chemical_list: D017382:Reactive Oxygen Species; D012906:Smoke; D013638:Tars; C024746:tobacco tar; D009538:Nicotine; D019255:NADPH Oxidases; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D002118:Calcium