INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Hydrogen peroxide regulates cell cycle progression in tumoral cells.
Autor/es:
GALLI S; CARRERAS MC; PODEROSO JJ
Lugar:
Buenos Aires
Reunión:
Congreso; XII Biennial Meeting of the Society for Free Radical Research International.; 2004
Institución organizadora:
Society for Free Radical Research International.
Resumen:
Mammalian cells express mitogen activated protein kinases (MAPKs) that integrate extracellular signals and transduction pathways, ending in specific responses (proliferation, cell cycle arrest, apoptosis). Mitochondria generates reactive oxygen species, implicated in physiological cell signaling. Hydrogen peroxide (H2O2) promotes tyrosine-phosphorylation of proteins, included ERK1/2 and p38. Steady-state H2O2 concentration ([H2O2]ss) depends on rates of mitochondrial production and degradation by cytosolic enzymes; proliferating tissues (fetal liver and brain) and tumors exhibit diminished [H2O2]ss, while quiescent tissues (adult liver) display two-fold higher [H2O2]ss. In this work we studied H2O2 modulation on cell cycle progression of tumoral cell line LP07. In these cells, 1 mM H2O2 promotes proliferation and higher doses (> 10mM) cell cycle arrest or apoptosis, with differential MAPKs phosphorylation. At 1 mM H2O2, activation of ERK1/2 is persistent while 50 mM H2O2 only induces transient ERK1/2 activation, with high and low of cyclin D1 expression, respectively. Inhibition of MEK1/2 limited cyclin D1 expression by 1 mM H2O2, indicating that the proliferative signal is driven by ERK1/2. Additionally, redox effects associated to ERK1/2 specific mitochondrial translocation and activation. These results suggest that persistent tumoral proliferation depends on differential activation and cellular traffic of MAPKs in connection with low [H2O2]ss in transformed cells.