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Microcin J25-Ga induces apoptosis in mammalian cells by inhibiting mitochondrial RNA-polymerase |
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| Authors: | Niklison-Chirou María V Dupuy Fernando Saavedra Lucila Hebert Elvira Banchio Claudia Minahk Carlos Morero Roberto D |
| Affiliation: | a Departamento de Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas (CONICET-UNT), Instituto de Química Biológica “Dr. Bernabe Bloj,” San Miguel de Tucumán, Argentina b Centro de Referencia para Lactobacilos (CERELA-CONICET), S.M. de Tucumán (T4000ILI), Argentina c Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Departamento de Ciencias Biológicas, Universidad Nacional de Rosario, Rosario, Argentina |
| Abstract: | MccJ25, an antimicrobial peptide, was unable to cause apoptosis of COS-7 cells in spite of inducing reactive-oxygen species overproduction as well as cytochrome c release from isolated mitochondria. Surprisingly, MccJ25-Ga, an amidated variant of MccJ25 that displays similar anti-mitochondrial effects, did induce apoptosis in COS-7. The only difference found between the activities of these peptides was the unpredicted inhibition of mitochondrial RNA synthesis by MccJ25-Ga. These results led us to hypothesize that both mitochondrial RNA polymerase and mitochondrial membrane might be the molecular targets of MccJ25-Ga in mitochondria and this combined effect may lead to apoptosis. |
| Keywords: | MccJ25, microcin J25 MccJ25-Ga, C-terminal amidated microcin J25 ROS, reactive oxygen species BSA, bovine serum albumin TCA, trichloroacetic acid ascorbic acid, vit C RNAP, RNA polymerase carboxy-H2DCFDA, 5-(-6)-carboxy-2&prime ,7&prime -dichloro-dihydrofluorescein diacetate LDH, lactate dehydrogenase CsA, cyclosporine A |
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