Activation of protein kinase C for protection of cells against apoptosis induced by the immunosuppressor prodigiosin.
Prodigiosin (PG) is a red pigment produced by Serratia marcescens with immunosuppressive activity. We had recently shown that PG-induced apoptosis in several cancer cell lines including Jurkat-T cells, while acting rapidly, potently and with no marked toxicity in non-malignant cells. Here we examine the role of protein kinase C (PKC) in the regulation of apoptosis triggered by PG. We evaluated the use of phorbol-myristate acetate (PMA) in the inhibition of apoptosis induced by PG in Jurkat-T cells by using FACS analysis of the phosphatidylserine externalisation, Hoechst 33342 staining and fragmentation pattern of DNA as well as proteolysis of poly-(ADP) ribose polymerase (PARP). The anti-apoptotic effect of PMA was accompanied by phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Pretreatment of cells with MEK inhibitor PD98059 inhibited PMA-induced phosphorylation of ERK1/2 and the cytoprotective ability of PMA. These results suggest that activation of PKC in Jurkat-T cells confer protection against apoptosis induced by PG and that ERK1/2 mediate anti-apoptotic PKC signaling.
Ramoneda
Beatriz Montaner
BM
Departament de Biologia Cellular i Anatomia Patològica, Cancer Cell Biology Research Group, Universitat de Barcelona, Feixa Llarga s/n, 08907 L'Hospitalet, Barcelona, Spain.
Pérez-Tomás
Ricardo
R
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis; D002273:Carcinogens / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011353:Prodigiosin / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D002273:Carcinogens; D005419:Flavonoids; D007166:Immunosuppressive Agents; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D011353:Prodigiosin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one