title: Induction of neurite-outgrowth in PC12 cells by alpha-toxin from Clostridium perfringens.
abstract: Alpha-toxin-induced phosphorylation of PDK1 via the tyrosine kinase A (TrkA) receptor signaling pathway plays an important role in the activation of rabbit neutrophils. The relation between the toxin and TrkA, however, remains poorly understood. Here, we show that the toxin-induced phosphorylation of TrkA is closely related to the induction of neurite-outgrowth in PC12 cells. The toxin induced neurite-outgrowth and phosphorylation of TrkA in the cells in a dose-dependent manner. K252a, a TrkA inhibitor, and shRNA for TrkA inhibited the toxin-induced neurite-outgrowth, and phosphorylation of TrkA and ERK1/2. PD98059, an inhibitor of the ERK1/2 cascade, inhibited phosphorylation of ERK1/2 and the neurite-outgrowth induced by alpha-toxin. The wild-type toxin induced the formation of diacylglycerol, and neurite-outgrowth, but H148G, a variant toxin which binds to cell membranes and has lost the enzymatic activity did not. We demonstrated that the phosphorylation of TrkA through the phospholipid metabolism induced by the toxin synergistically play a key role in neurite-outgrowth.
authors: Department of Microbiology, Faculty of Pharmaceutical Science, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. masa@ph.bunri-u.ac.jp
authors: Masataka
authors: M
authors: Oda
authors: Yuki
authors: Y
authors: Saito
authors: Yuka
authors: Y
authors: Morimune
authors: Masahiro
authors: M
authors: Nagahama
authors: Jun
authors: J
authors: Sakurai
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D016501:Neurites / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D016716:PC12 Cells; D010743:Phospholipids / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D005419:Flavonoids; D010743:Phospholipids; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D020917:Receptor, trkA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one