title: A proteomic analysis of the early secondary molecular effects caused by Cn2 scorpion toxin on neuroblastoma cells.
abstract: Although the primary physiological effects produced by scorpion toxins are already well known, most of the secondary molecular events following scorpion neurotoxins-ion channel interactions are poorly understood and described. For this reason, we used a proteomic approach to determine the changes in relative protein abundance in F11 mouse neuroblastoma cells treated with Cn2, the major β-toxin from the venom of the scorpion Centruroides noxius Hoffmann. Here we show that the relative abundance of 24 proteins changed after Cn2 treatment. Proteins related to protection from apoptosis and cell survival, as well as those involved in cell morphology and some translation elongation factors were diminished. By contrast, proteins associated with energy metabolism were increased. Additionally, results of western immunoblots confirmed the preference of action towards some special targets. These results suggest that Cn2 could modify the neuronal structure and induce apoptosis and reduction of the proliferation and cell survival. To support this conclusion we directly measured the Cn2 effect on cell proliferation, division and apoptosis. Our results open new avenues for continuing the studies aimed at better understanding the envenomation process caused by scorpion stings.
  
  
  CONCLUSIONS
  The purpose of this work was to identify which proteins, apart from the ion-channels, are involved in the envenomation process in order to develop possible strategies to circumvent the deleterious effects caused by the toxic peptides of the venom. For this reason, we characterized the early changes in the proteome of F11 cells induced by Cn2, the major toxin of the New World scorpion C. noxius Hoffmann, using 2D-PAGE and LC-MS/MS. We identified 24 proteins which relative abundance is modified after the Cn2 treatment. Among these, proteins related with apoptosis protection, cell survival, neuronal morphology and some translation elongation factors were diminished, whereas proteins associated with energy metabolism were increased.
authors.affiliation: Departmento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Avenida Universidad Nacional Autonoma de Mexico, Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, Cuernavaca 62210, Mexico.
authors.forename: Martha Pedraza
authors.initials: MP
authors.lastname: Escalona
authors.affiliation: Laboratorio Universitario de Proteomica, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, Cuernavaca 62210, Mexico.
authors.forename: Cesar V F
authors.initials: CV
authors.lastname: Batista
authors.affiliation: Departmento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Avenida Universidad Nacional Autonoma de Mexico, Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, Cuernavaca 62210, Mexico.
authors.forename: Rita Restano
authors.initials: RR
authors.lastname: Cassulini
authors.affiliation: Departmento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Avenida Universidad Nacional Autonoma de Mexico, Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, Cuernavaca 62210, Mexico.
authors.forename: Marisol Sandoval
authors.initials: MS
authors.lastname: Rios
authors.affiliation: Departmento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Avenida Universidad Nacional Autonoma de Mexico, Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, Cuernavaca 62210, Mexico.
authors.forename: Fredy I
authors.initials: FI
authors.lastname: Coronas
authors.affiliation: Departmento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Avenida Universidad Nacional Autonoma de Mexico, Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, Cuernavaca 62210, Mexico. Electronic address: possani@ibt.unam.mx.
authors.forename: Lourival D
authors.initials: LD
authors.lastname: Possani
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D015180:Electrophoresis, Gel, Two-Dimensional; D004594:Electrophysiology; D057809:HEK293 Cells; D006736:Horses; D006801:Humans; D007525:Isoelectric Focusing; D013058:Mass Spectrometry; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000737:chemistry; D040901:Proteomics; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry; D012605:Scorpions; D012756:Sheep; D053719:Tandem Mass Spectrometry
chemical_list: D011506:Proteins; D012604:Scorpion Venoms
keywords: Bidimensional gel; Cellular events; Mass spectrometry; Proteomic analysis; Scorpion toxin