Peptide gomesin triggers cell death through L-type channel calcium influx, MAPK/ERK, PKC and PI3K signaling and generation of reactive oxygen species

Peptide gomesin triggers cell death through L-type channel calcium influx, MAPK/ERK, PKC and PI3K signaling and generation of reactive oxygen species

Author Soletti, Rossana C. Google Scholar
del Barrio, Laura Google Scholar
Daffre, Sirlei Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Borges, Helena L. Google Scholar
Moura-Neto, Vivaldo Google Scholar
Lopez, Manuela G. Google Scholar
Gabilan, Nelson H. Google Scholar
Institution Univ Autonoma Madrid
Universidade Federal de Santa Catarina (UFSC)
Universidade Federal do Rio de Janeiro (UFRJ)
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Gomesin is an antimicrobial peptide isolated from hemocytes of a common Brazilian tarantula spider named Acanthoscurriagomesiana. This peptide exerts antitumor activity in vitro and in vivo by an unknown mechanism. in this study, the cytotoxic mechanism of gomesin in human neuroblastoma SH-SY5Y and rat pheochromocytoma PC12 cells was investigated. Gomesin induced necrotic cell death and was cytotoxic to SH-SY5Y and PC12 cells. the peptide evoked a rapid and transient elevation of intracellular calcium levels in Fluo-4-AM loaded PC12 cells, which was inhibited by nimodipine, an L-type calcium channel blocker. Preincubation with nimodipine also inhibited cell death induced by gomesin in SH-SY5Y and PC12 cells. Gomesin-induced cell death was prevented by the pretreatment with MAPK/ERK, PKC or PI3K inhibitors, but not with PKA inhibitor. in addition, gomesin generated reactive oxygen species (ROS) in SH-SY5Y cells, which were blocked with nimodipine and MAPK/ERK, PKC or PI3K inhibitors. Taken together, these results suggest that gomesin could be a useful anticancer agent, which mechanism of cytotoxicity implicates calcium entry through L-type calcium channels, activation of MAPK/ERK, PKC and PI3K signaling as well as the generation of reactive oxygen species. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
Keywords Gomesin
Antimicrobial peptides
Cytotoxicity
Calcium channels
Cell signaling
Necrosis
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
FINEP
Spanish Agencies
Ministerio de Educacion y Ciencia
Fundacion Carolina, Universidad Autonoma de Madrid
Fundacion Teofilo Hernando
Grant number CAPES: 0013/01-3
CAPES: 173/2008
FINEP: 01.06.0842-00
Ministerio de Educacion y Ciencia: SAF2006-08540
Ministerio de Educacion y Ciencia: PHB2007-0004-PC
Date 2010-07-30
Published in Chemico-biological Interactions. Clare: Elsevier B.V., v. 186, n. 2, p. 135-143, 2010.
ISSN 0009-2797 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 135-143
Origin http://dx.doi.org/10.1016/j.cbi.2010.04.012
Access rights Closed access
Type Article
Web of Science ID WOS:000279644900005
URI http://repositorio.unifesp.br/handle/11600/32737

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