In recent years, the antitumoral activity of antimicro
bial 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 Ca
2+ signaling during Gm-induced cell death. The results indicated that Gm
binds to the plasma mem
brane and rapidly translocates into the cytoplasm. Moreover, 20 渭M Gm increases the cytosolic Ca
2+ and induces mem
brane permea
bilization after 30 min of treatment. Direct Ca
2+ measurements in CHO cells transfected with the genetically encoded D1-cameleon to the endoplasmic reticulum (ER) revealed that Gm induces ER Ca
2+ depletion, which in turn resulted in oscillatory mitochondrial Ca
2+ signal, as measured in cells expressing the genetically encoded pro
be to the mitochondrial matrix
b>mitb>Pericam. This leads to mitochondria disruption, loss of mitochondrial mem
brane potential and increased reactive oxygen species prior to mem
brane permea
bilization. Gm-induced mem
brane permea
bilization
by a Ca
2+-dependent pathway involving Gm translocation into the cell, ER Ca
2+ depletion and disruption, mitochondrial Ca
2+ overload and oxidative stress.<
br>
Keywords:
bs.acs.org/action/doSearch?action=search&searchText=antimicrobial+peptide&qsSearchArea=searchText">antimicrobial peptide; bs.acs.org/action/doSearch?action=search&searchText=gomesin&qsSearchArea=searchText">gomesin; bs.acs.org/action/doSearch?action=search&searchText=membrane+permeabilization&qsSearchArea=searchText">membrane permeabilization; bs.acs.org/action/doSearch?action=search&searchText=calcium&qsSearchArea=searchText">calcium; bs.acs.org/action/doSearch?action=search&searchText=endoplasmic+reticulum&qsSearchArea=searchText">endoplasmic reticulum; bs.acs.org/action/doSearch?action=search&searchText=mitochondria&qsSearchArea=searchText">mitochondria