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Paredes-Gamero 2012 Mol Pharm

From Bioblast
Publications in the MiPMap
Paredes-Gamero EJ, Casaes-Rodrigues RL, Moura GE, Domingues TM, Buri MV, Ferreira VH, Trindade ES, Moreno-Ortega AJ, Cano-Abad MF, Nader HB, Ferreira AT, Miranda A, Justo GZ, Tersariol IL (2012) Cell-permeable gomesin peptide promotes cell death by intracellular Ca2+ overload. Mol Pharm 9:2686-97.

ยป PMID: 22873645

Paredes-Gamero EJ, Casaes-Rodrigues RL, Moura GE, Domingues TM, Buri MV, Ferreira VH, Trindade ES, Moreno-Ortega AJ, Cano-Abad MF, Nader HB, Ferreira AT, Miranda A, Justo GZ, Tersariol IL (2012) Mol Pharm

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 ฮผM 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.


Labels: MiParea: mt-Membrane