Hyperosmotic stress-dependent NFkappaB activation is regulated by reactive oxygen species and IGF-1 in cultured cardiomyocytes.
We have recently shown that hyperosmotic stress activates p65/RelB NFkappaB in cultured cardiomyocytes with dichotomic actions on caspase activation and cell death. It remains unexplored how NFkappaB is regulated in cultured rat cardiomyocytes exposed to hyperosmotic stress. We study here: (a) if hyperosmotic stress triggers reactive oxygen species (ROS) generation and in turn whether they regulate NFkappaB and (b) if insulin-like growth factor-1 (IGF-1) modulates ROS production and NFkappaB activation in hyperosmotically-stressed cardiomyocytes. The results showed that hyperosmotic stress generated ROS in cultured cardiac myocytes, in particular the hydroxyl and superoxide species, which were inhibited by N-acetylcysteine (NAC). Hyperosmotic stress-induced NFkappaB activation as determined by IkappaBalpha degradation and NFkappaB DNA binding. NFkappaB activation and procaspase-3 and -9 fragmentation were prevented by NAC and IGF-1. However, this growth factor did not decrease ROS generation induced by hyperosmotic stress, suggesting that its actions over NFkappaB and caspase activation may be due to modulation of events downstream of ROS generation. We conclude that hyperosmotic stress induces ROS, which in turn activates NFkappaB and caspases. IGF-1 prevents NFkappaB activation by a ROS-independent mechanism.
Eisner
Verónica
V
Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago 8380492, Chile.
Criollo
Alfredo
A
Quiroga
Clara
C
Olea-Azar
Claudio
C
Santibañez
Juan Francisco
JF
Troncoso
Rodrigo
R
Chiong
Mario
M
Díaz-Araya
Guillermo
G
Foncea
Rocío
R
Lavandero
Sergio
S
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D007334:Insulin-Like Growth Factor I; D020169:Caspases; D000111:Acetylcysteine