title: Activation of PKC is sufficient to induce an apoptotic program in salivary gland acinar cells.
abstract: Accumulating evidence suggests that specific isoforms of PKC may function to promote apoptosis. We show here that activation of the conventional and novel isoforms of PKC with 12-O-tetradecanoyl phorbol-13- ester (TPA) induces apoptosis in salivary acinar cells as indicated by DNA fragmentation and activation of caspase-3. TPA-induced DNA fragmentation, caspase-3 activation, and morphologic indicators of apoptosis, can be enhanced by pretreatment of cells with the calpain inhibitor, calpeptin, prior to the addition of TPA. Analysis of PKC isoform expression by immunoblot shows that TPA-induced downregulation of PKC alpha and PKC delta is delayed in cells pre-treated with calpeptin, and that this correlates with an increase of these isoforms in the membrane fraction of cells. TPA-induced apoptosis is accompanied by biphasic activation of the c-jun-N-terminal kinase (JNK) pathway and inactivation of the extracellular regulated kinase (ERK) pathway. Expression of constitutively activated PKC alpha or PKC delta, but not kinase negative mutants of these isoforms, or constitutively activated PKC epsilon, induces apoptosis in salivary acinar cells, suggesting a role for these isoforms in TPA-induced apoptosis. These studies demonstrate that activation of PKC is sufficient for initiation of an apoptotic program in salivary acinar cells. Cell Death and Differentiation (2000) 7, 1200 - 1209.
authors.affiliation: Department of Basic Science and Oral Research, School of Dentistry, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado, CO 80262, USA. mary.reyland@uchsc.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Reyland
authors.forename: K A
authors.initials: KA
authors.lastname: Barzen
authors.forename: S M
authors.initials: SM
authors.lastname: Anderson
authors.forename: D O
authors.initials: DO
authors.lastname: Quissell
authors.forename: A A
authors.initials: AA
authors.lastname: Matassa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002273:Carcinogens / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002273:Carcinogens; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D020033:Protein Isoforms; C071482:calpeptin; D011493:Protein Kinase C; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D013755:Tetradecanoylphorbol Acetate