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

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

Author Paredes-Gamero, Edgar J. Autor UNIFESP Google Scholar
Casaes-Rodrigues, Rafael L. Autor UNIFESP Google Scholar
Moura, Gioconda E. D. D. Autor UNIFESP Google Scholar
Domingues, Tatiana Moreira Autor UNIFESP Google Scholar
Buri, Marcus V. Autor UNIFESP Google Scholar
Ferreira, Victor H. C. Google Scholar
Trindade, Edvaldo S. Google Scholar
Moreno-Ortega, Ana J. Google Scholar
Cano-Abad, Maria F. Google Scholar
Nader, Helena B. Autor UNIFESP Google Scholar
Ferreira, Alice T. Autor UNIFESP Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Justo, Giselle Z. Autor UNIFESP Google Scholar
Tersariol, Ivarne L. S. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Fed Parana
Univ Autonoma Madrid
Univ Mogi das Cruzes
Abstract In 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.
Keywords antimicrobial peptide
membrane permeabilization
endoplasmic reticulum
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Consolodacion de grupos UAM-CAM
FPU from Ministerio de Educacion, Spain
Grant number FAPESP: 2009/54869-2
Consolodacion de grupos UAM-CAM: 1004040047
FPU from Ministerio de Educacion, Spain: AP2009-0343
Date 2012-09-01
Published in Molecular Pharmaceutics. Washington: Amer Chemical Soc, v. 9, n. 9, p. 2686-2697, 2012.
ISSN 1543-8384 (Sherpa/Romeo, impact factor)
Publisher Amer Chemical Soc
Extent 2686-2697
Origin http://dx.doi.org/10.1021/mp300251j
Access rights Closed access
Type Article
Web of Science ID WOS:000308263700032
URI http://repositorio.unifesp.br/handle/11600/35242

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