Cell-Permeable Gomesin Peptide Promotes Cell Death by Intracellular Ca2+ Overload

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dc.contributor.authorParedes-Gamero, Edgar J. [UNIFESP]
dc.contributor.authorCasaes-Rodrigues, Rafael L. [UNIFESP]
dc.contributor.authorMoura, Gioconda E. D. D. [UNIFESP]
dc.contributor.authorDomingues, Tatiana Moreira [UNIFESP]
dc.contributor.authorBuri, Marcus V. [UNIFESP]
dc.contributor.authorFerreira, Victor H. C.
dc.contributor.authorTrindade, Edvaldo S.
dc.contributor.authorMoreno-Ortega, Ana J.
dc.contributor.authorCano-Abad, Maria F.
dc.contributor.authorNader, Helena B. [UNIFESP]
dc.contributor.authorFerreira, Alice T. [UNIFESP]
dc.contributor.authorMiranda, Antonio [UNIFESP]
dc.contributor.authorJusto, Giselle Z. [UNIFESP]
dc.contributor.authorTersariol, Ivarne L. S. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed Parana
dc.contributor.institutionUniv Autonoma Madrid
dc.contributor.institutionUniv Mogi das Cruzes
dc.date.accessioned2016-01-24T14:27:39Z
dc.date.available2016-01-24T14:27:39Z
dc.date.issued2012-09-01
dc.description.abstractIn recent years, the antitumoral activity of antimicrobial peptides (AMPs) has been the goal of many research studies. Among AMPs, gomesin (Gm) displays antitumor activity by unknown mechanisms. Herein, we studied the cytotoxicity of Gm in the Chinese hamster ovary (CHO) cell line. Furthermore, we investigated the temporal ordering of organelle changes and the dynamics of Ca2+ signaling during Gm-induced cell death. the results indicated that Gm binds to the plasma membrane and rapidly translocates into the cytoplasm. Moreover, 20 mu M Gm increases the cytosolic Ca2+ and induces membrane permeabilization after 30 min of treatment. Direct Ca2+ measurements in CHO cells transfected with the genetically encoded D1-cameleon to the endoplasmic reticulum (ER) revealed that Gm induces ER Ca2+ depletion, which in turn resulted in oscillatory mitochondrial Ca2+ signal, as measured in cells expressing the genetically encoded probe to the mitochondrial matrix (mit)Pericam. This leads to mitochondria disruption, loss of mitochondrial membrane potential and increased reactive oxygen species prior to membrane permeabilization. Gm-induced membrane permeabilization by a Ca2+-dependent pathway involving Gm translocation into the cell, ER Ca2+ depletion and disruption, mitochondrial Ca2+ overload and oxidative stress.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Fed Parana, Dept Biol Celular, BR-81531990 Curitiba, Parana, Brazil
dc.description.affiliationUniv Autonoma Madrid, Inst Teofilo Hernando, Inst Invest Sanitaria, Hosp Univ Princesa,Serv Farmacol Clin, Madrid, Spain
dc.description.affiliationUniversidade Federal de São Paulo, Dept Ciencias Biol, Diadema, SP, Brazil
dc.description.affiliationUniv Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, Mogi Das Cruzes, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Ciencias Biol, Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConsolodacion de grupos UAM-CAM
dc.description.sponsorshipFPU from Ministerio de Educacion, Spain
dc.description.sponsorshipIDFAPESP: 2009/54869-2
dc.description.sponsorshipIDConsolodacion de grupos UAM-CAM: 1004040047
dc.description.sponsorshipIDFPU from Ministerio de Educacion, Spain: AP2009-0343
dc.format.extent2686-2697
dc.identifierhttp://dx.doi.org/10.1021/mp300251j
dc.identifier.citationMolecular Pharmaceutics. Washington: Amer Chemical Soc, v. 9, n. 9, p. 2686-2697, 2012.
dc.identifier.doi10.1021/mp300251j
dc.identifier.issn1543-8384
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35242
dc.identifier.wosWOS:000308263700032
dc.language.isoeng
dc.publisherAmer Chemical Soc
dc.relation.ispartofMolecular Pharmaceutics
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectantimicrobial peptideen
dc.subjectgomesinen
dc.subjectmembrane permeabilizationen
dc.subjectcalciumen
dc.subjectendoplasmic reticulumen
dc.subjectmitochondriaen
dc.titleCell-Permeable Gomesin Peptide Promotes Cell Death by Intracellular Ca2+ Overloaden
dc.typeinfo:eu-repo/semantics/article
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