Interferon-alpha2b (IFN-alpha2b)-induced apoptosis is mediated by p38 MAPK in hepatocytes from rat preneoplastic liver via activation of NADPH oxidase.

Autor: Quiroga AD; Facultad de Ciencias Bioquimicas y Farmaceuticas, Instituto de Fisiologia Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Universidad Nacional de Rosario, Rosario, Argentina., de Lujan Alvarez M, Parody JP, Ronco MT, Carnovale CE, Carrillo MC
Jazyk: angličtina
Zdroj: Growth factors (Chur, Switzerland) [Growth Factors] 2009 Aug; Vol. 27 (4), pp. 214-27.
DOI: 10.1080/08977190902951558
Abstrakt: It is still unclear how Interferon-alfa (IFN-alpha) acts on preventing the appearance of hepatocarcinogenesis. We have demonstrated that IFN-alpha2b induces hepatocytic transforming growth factor-beta1 (TGF-beta(1)) production and secretion by inducing reactive oxygen species (ROS) formation through the activation of NADPH oxidase. This TGF-beta(1), alters antioxidant defences and induces programmed cell death. Since it was demonstrated that IFN-alpha induces apoptosis through the activation of p38 mitogen-activated protein kinase (p38 MAPK), this study was aimed to assess the role of this kinase in the IFN-alpha2b-induced apoptosis in rat liver preneoplasia; and to further evaluate the participation of NADPH oxidase. p38 MAPK pathway was activated during the IFN-alpha2b-induced apoptosis in rat liver preneoplasia. This activation was accompanied with phosphorylation of different transcription factors, depending on the time of IFN-alpha2b stimulus. Our data suggest that NADPH oxidase is activated by IFN-alpha2b through p38 MAPK. p38 MAPK-induced activation of NADPH oxidase is accomplished by a two-step pathway: first, ROS-independent and second ROS- and TGF-beta(1)-dependent.
Databáze: MEDLINE
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