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Redox Modulation of the Apoptogenic Activity of Thapsigargin
Author(s) -
CERELLA CLAUDIA,
COPPOLA SIMONA,
D'ALESSIO MARIA,
DE NICOLA MILENA,
MAGRINI ANDREA,
BERGAMASCHI ANTONIO,
GHIBELLI LINA
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1387.028
Subject(s) - thapsigargin , chemistry , radical , nitric oxide , endoplasmic reticulum , apoptosis , redox , reactive oxygen species , glutathione , oxygen , biochemistry , enzyme , inorganic chemistry , organic chemistry
Thapsigargin (THG), a selective inhibitor of endoplasmic reticulum (ER) Ca 2+ ‐ATPases, causes the rapid emptying of ER Ca 2+ ; in some cell types, this is accompanied by apoptosis, whereas other cells maintain viability. In order to understand the molecular determinants of such a different behavior, we explored the role of oxygen versus nitrogen radicals, by analyzing the apoptogenic ability of THG in the presence of inhibitors of glutathione or nitric oxide (NO) synthesis, respectively. We observed that oxygen radicals play a sensitizing role whereas nitrogen radicals prevent THG‐dependent apoptosis, showing that the apoptogenic effect of THG is redox sensitive.