title: Hyperosmotic stress-dependent NFkappaB activation is regulated by reactive oxygen species and IGF-1 in cultured cardiomyocytes.
abstract: 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.
authors.affiliation: Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago 8380492, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: Eisner
authors.forename: Alfredo
authors.initials: A
authors.lastname: Criollo
authors.forename: Clara
authors.initials: C
authors.lastname: Quiroga
authors.forename: Claudio
authors.initials: C
authors.lastname: Olea-Azar
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Santibañez
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Troncoso
authors.forename: Mario
authors.initials: M
authors.lastname: Chiong
authors.forename: Guillermo
authors.initials: G
authors.lastname: Díaz-Araya
authors.forename: Rocío
authors.initials: R
authors.lastname: Foncea
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
mesh_terms: 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*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D007334:Insulin-Like Growth Factor I; D020169:Caspases; D000111:Acetylcysteine