Jararhagin, a snake venom metalloprotease-disintegrin, activates the Rac1 GTPase and stimulates neurite outgrowth in neuroblastoma cells

It has been shown previously that the snake venom metalloprotease-disintegrin jararhagin stimulates cell migration and cytoskeletal rearrangement, independently of its effects on cellular adhesion but possibly associated with the activation of small GTP-binding proteins from the Rho family [Costa, E...

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Bibliographic Details
Published in:Toxicon (Oxford) 2008-08, Vol.52 (2), p.380-384
Main Authors: Costa, Erica Pereira, Del Debbio, Carolina Beltrame, Cintra, Leandro Carrijo, da Fontoura Costa, Luciano, Hamassaki, Dânia Emi, Santos, Marinilce Fagundes
Format: Article
Language:English
Subjects:
Actin
Animal poisons toxicology. Antivenoms
Animals
Biological and medical sciences
Bothrops - physiology
Bothrops jararaca Venom
Cell Adhesion - drug effects
Cell Line, Tumor
Crotalid Venoms - toxicity
Cytoskeleton
Medical sciences
Metalloendopeptidases - toxicity
Microscopy, Confocal
Neurites - drug effects
Neurites - metabolism
Neurites - pathology
Neuro-2a
Neuroblastoma - drug therapy
Neuroblastoma - metabolism
Neuroblastoma - pathology
Neurology
Neuronal differentiation
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Platelet Aggregation Inhibitors - toxicity
rac1 GTP-Binding Protein - metabolism
Toxicology
Toxin
Tumors of the nervous system. Phacomatoses
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Summary:It has been shown previously that the snake venom metalloprotease-disintegrin jararhagin stimulates cell migration and cytoskeletal rearrangement, independently of its effects on cellular adhesion but possibly associated with the activation of small GTP-binding proteins from the Rho family [Costa, E.P., Santos, M.F., 2004. Toxicon 44(8), 861–870.] Here we show that jararhagin stimulates spreading, actin dynamics and neurite outgrowth in neuroblastoma cells, and that this effect is accompanied by the translocation of the Rac1 small GTPase to the membrane fraction, suggesting its activation. Stimulation of neurite outgrowth was observed within minutes and was dependent on the proteolytic activity of the toxin. These results suggest that jararhagin may stimulate neuronal differentiation, being a potential tool for neuronal regeneration studies.
ISSN:0041-0101
1879-3150
DOI:10.1016/j.toxicon.2008.04.165