INVESTIGADORES
QUIROGA Ariel Dario
artículos
Título:
Interferon-a2b (IFN-a2b)-induced apoptosis is mediated by p38 MAPK in hepatocytes from rat preneoplastic liver via activation of NADPH oxidase
Autor/es:
QUIROGA, ARIEL DARIO; ALVAREZ, MARIA DE LUJAN; PARODY, JUAN PABLO; RONCO, MARIA TERESA; CARNOVALE, CRISTINA ESTER; CARRILLO, MARÍA CRISTINA
Revista:
GROWTH FACTORS
Editorial:
TAYLOR & FRANCIS LTD
Referencias:
Año: 2009 p. 1 - 14
ISSN:
0897-7194
Resumen:
It
is still unclear how Interferon-alfa (IFN-a) acts on preventing the appearance
of hepatocarcinogenesis. We havedemonstrated that IFN-a2b induces hepatocytic
transforming growth factor-beta1 (TGF-b1) production and secretion by inducing
reactive oxygen species (ROS) formation through the activation of NADPH
oxidase. This TGF-b1, altersantioxidant defences and induces programmed cell
death. Since it was demonstrated that IFN-a 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-a2b-induced apoptosis in rat
liver preneoplasia; and to further evaluate the participation of NADPH oxidase.
p38 MAPK pathway was activated during the IFN-a2b-induced apoptosis in rat
liver preneoplasia. This activation was accompanied with phosphorylation of
different transcription factors, depending on the time of IFN-a2b stimulus. Our
data suggest that NADPH oxidase is activated by IFN-a2b 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-b1-dependent.