Toxin-induced activation of Rho GTP-binding protein increases Bcl-2 expression and influences mitochondrial homeostasis.
It is now well established that apoptosis plays a pivotal role in several physiological and pathological situations. Consequently, the mechanisms controlling the cell fate are currently the subject of intense investigation. In this work, we report that an Escherichia coli protein toxin (Cytotoxic Necrotizing Factor 1, CNF1) which activates the Rho GTP-binding protein and prevent apoptosis in epithelial cells was able to: (i) influence the mitochondrial homeostasis and (ii) modulate the expression of proteins belonging to the Bcl-2 family. In particular, the content of the antiapoptotic products Bcl-2 and Bcl-XL resulted to be increased in treated cells, whereas the expression of the proapoptotic protein Bax remained unaltered. CNF1 induces cell spreading via activation of Rho and cell spreading has been reported to promote cell survival. Cytochalasin B, which provokes most of the morphological changes typical of CNF1, including cell spreading, but without the involvement of Rho, was unable to counteract apoptosis. Altogether our results suggest a link between the Rho GTP-binding protein and the regulation of the mitochondrial homeostasis via an effect on the antiapoptotic proteins of the Bcl-2 family.
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy. fiorentini@ul.net.iss.it
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Fiorentini
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Matarrese
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Straface
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Falzano
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Fabbri
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Donelli
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Cossarizza
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Boquet
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Malorni
D017209:Apoptosis / Q000502:physiology; D001427:Bacterial Toxins / Q000494:pharmacology*; D002460:Cell Line; D048429:Cell Size; D003571:Cytochalasin B / Q000494:pharmacology; D003603:Cytotoxins / Q000494:pharmacology*; D004847:Epithelial Cells; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D020742:rhoA GTP-Binding Protein
D001427:Bacterial Toxins; D003603:Cytotoxins; D029968:Escherichia coli Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C060296:cytotoxic necrotizing factor type 1; D003571:Cytochalasin B; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein