Redox modulation of the apoptogenic activity of thapsigargin.
Thapsigargin (THG), a selective inhibitor of endoplasmic reticulum (ER) Ca2+-ATPases, causes the rapid emptying of ER Ca2+; 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.
Cerella
Claudia
C
Dipartimento di Biologia, Universita' di Roma Tor Vergata, via Ricerca Scientifica, 1, 00133 Roma (I), Italy.
Coppola
Simona
S
D'Alessio
Maria
M
De Nicola
Milena
M
Magrini
Andrea
A
Bergamaschi
Antonio
A
Ghibelli
Lina
L
D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D010084:Oxidation-Reduction; D019284:Thapsigargin / Q000494:pharmacology*; D020298:U937 Cells
D019284:Thapsigargin