INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Mitochondrial nitric oxide synthase and redox signaling
Autor/es:
CARRERAS MC; FINOCCHIETTO P; CONVERSO D; LABATO M; FRANCO MC; GALLI S; PODEROSO JJ
Lugar:
Cádiz, España
Reunión:
Congreso; Oxygen Club of California. Oxidants and Antioxidants in Biology.; 2003
Institución organizadora:
Oxygen Club of California.
Resumen:
It is noteworthy that changes in the expression and activity of constitutive mtNOS will be followed by significant variations in matrix NO steady-state levels in the relatively small and welldifferentiated mitochondrial compartment (Giulivi et al, 1998). The mitochondrial utilization of NO involves the production of superoxide anion and hydrogen peroxide (H2O2) a species freely diffusible outside the mitochondria (Poderoso et al, 1996 and 1999, Antunez and Cadenas, 2000). In the last years, cumulative evidence showed that H2O2 production and the consequent oxidative stress level play an important role in the activation of signaling molecules which control the complex machinery involved in cell proliferation, differentiation, apoptosis, senescence, cell transformation and cancer (Davies 2000, Huang et al, 2000). On this basis, it was interesting to analyze the modulation of mtNOS in the frame of cellular redox state and cell cycle progression. These variables were then followed in normal quiescent tissues, in proliferating ones, in tumoral tissues and in transformed cell lines. Collectively, the data show that a) normal proliferating tissues like developing brain or liver have substantially less mtNOS content and mitochondrial H2O2 yield than quiescent non-proliferating tissues b) transition of proliferation to tissue differentiation involves a relatively rapid mtNOS increase. Conversely, liver proliferation induced by a single T4 dose is followed by a marked and transient decrease of mtNOS. In addition, tumoral cells exhibit very low mtNOS activity and H2O2. Therefore, cascades like D cyclins and MAPKs responding to H2O2 result ultimately modulated by changes in mtNOS, which may constitute a platform contributing to persistent cell proliferation or to cell cycle arrest.