Signal transduction pathways and cellular intoxication with Clostridium difficile toxins

✍ Scribed by Maria Caspar Shoshan; Carla Fiorentini; Monica Thelestam

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 778 KB
• Volume: 52
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240520114

✦ Synopsis

In cultured cells the cytopathic effects (CPE) of Clostrrdrurn drfficrle toxins A and B are superficially similar The irreversible CPEs involve a reorganization of the cytoskeleton, but the molecular details of the mechanism(s) of action are unknown As part of the work to elucidate the events leading to the CPE, cultured cells were preincubated with agents known to either stimulate or inhibit some major signal transduction pathways, whereupon toxin was added and the development of the CPE was followed. Both toxin-induced CPEs were enhanced by phorbol esters and mezerein, which stimulate protein kinase C, while they were inhibited by the phospholipase A2 inhibitors quinacrine and 4-bromophenacylbromide Agents affecting certain G-proteins, cGMP and CAMP levels, phosphatases, prostacyclin, Iipoxygenase, and phospholipase C did not affect the development of the CPE of either toxin Thus, the cytoskeletal effect induced by toxins A or B appears to require PLA2 activity and involves at least part of a protein kinase C-dependent pathway, but not pertussis toxin-sensitive G-proteins, cyclic nucleotides, eicosanoid metabolites, or phospholipase C activity In addition, both toxins were shown to activate phospholipase A2.