tailieunhanh - Báo cáo khoa học: Microcin J25 induces the opening of the mitochondrial transition pore and cytochrome c release through superoxide generation

Microcin J25, an antimicrobial lasso-structure peptide, induces the opening of mitochondrial permeability transition pores and the subsequent loss of cytochromec. The microcin J25 effect is mediated by the stimulation of superoxide anion overproduction. An increased uptake of calcium is also involved in this process. | ễFEBS Journal Microcin J25 induces the opening of the mitochondrial transition pore and cytochrome c release through superoxide generation Maria Niklison Chirou Augusto Bellomio Fernando Dupuy Beatriz Arcuri Carlos Minahk and Roberto Morero Departamento de Bioquimica de la Nutricion Institute Superior de Investigaciones Biologicas Consejo Nacionalde Investigaciones Cientificas y Tecnicas Universidad Nacionalde Tucuman Instituto de Quimica Biologica Dr. Bernabe Bloj San Miguelde Tucuman Argentina Keywords antibiotics Ca2 cytochrome c microcin mitochondria Correspondence R. Morero Chacabuco 461 S. M. de Tucuman 4000 Argentina Fax 54 0381 4248025 Tel 54 0381 4248921 E-mail rdmorero@ Received 23 April2008 revised 21 May 2008 accepted 12 June 2008 Microcin J25 an antimicrobial lasso-structure peptide induces the opening of mitochondrial permeability transition pores and the subsequent loss of cytochrome c. The microcin J25 effect is mediated by the stimulation of superoxide anion overproduction. An increased uptake of calcium is also involved in this process. Additional studies with superoxide dismutase ascorbic acid and different specific inhibitors such as ruthenium red cyclosporin A and Mn2 allowed us to establish a time sequence of events starting with the binding of microcin J25 followed by superoxide anion overproduction opening of mitochondrial permeability transition pores mitochondrial swelling and the concomitant leakage of cytochrome c. doi Microcin J25 MccJ25 a 21-amino acid antimicrobial peptide that is active against certain human pathogens such as Salmonella and Shigella 1 has an unusual lasso distinctive structure 2-4 and a dual mechanism of action. Microcin J25 inhibits transcription by obstructing the RNA polymerase secondary channel 5 and affects independently the cytoplasmic membrane of Escherichia coli and Salmonella enterica serovars 6 . In this regard it was shown that MccJ25 disrupts the membrane .