Electron paramagnetic resonance and kinetics experiments have been made to determine the formation, stability, and fate of the natural nitric oxide carrier, dinitrosyl-diglutathionyl-iron complex (DNDGIC), in heterogeneous systems approaching in vivo conditions. Both in human placenta and rat liver homogenates DNDGIC is formed spontaneously from GSH, S-nitroso-glutathione, and trace amounts of ferrous ions. DNDGIC is unstable in homogenates depleted of glutathione S-transferase (GST); an initial phase of rapid decomposition is followed by a slower decay, which is inversely proportional to the concentration. In the crude human placenta homogenate, GSTP1-1, which represents 90% of the cytosolic GST isoenzymes, is the preferential target for DNDGIC. It binds the complex almost stoichiometrically and stabilizes it for several hours (t1/2 = 8 h). In the presence of an excess of DNDGIC, negative cooperativity in GSTP1-1 opposes the complete loss of the usual detoxicating activity of this enzyme. In the rat liver homogenate, multiple endogenous GSTs (mainly Alpha and Mu class isoenzymes) bind the complex quantitatively and stabilize it (t1/2 = 4.5 h); negative cooperativity is also seen for these GSTs. Thus, the entire pool of cytosolic GSTs, with the exception of the Theta GST, represents a target for stoichiometric amounts of DNDGIC and may act as storage proteins for nitric oxide. These results confirm the existence of a cross-link between NO metabolism and the GST superfamily.

Turella, P., Pedersen, J.z., Caccuri, A.m., De Maria, F., Mastroberardino, P., LO BELLO, M., et al. (2003). Glutathione transferase superfamily behaves like storage proteins for dinitrosyl-diglutathionyl-iron complex in heterogeneous systems. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 278(43), 42294-42299 [10.1074/jbc.M305569200].

Glutathione transferase superfamily behaves like storage proteins for dinitrosyl-diglutathionyl-iron complex in heterogeneous systems

PEDERSEN, JENS ZACHO;CACCURI, ANNA MARIA;LO BELLO, MARIO;FEDERICI, GIORGIO;RICCI, GIORGIO
2003-10-24

Abstract

Electron paramagnetic resonance and kinetics experiments have been made to determine the formation, stability, and fate of the natural nitric oxide carrier, dinitrosyl-diglutathionyl-iron complex (DNDGIC), in heterogeneous systems approaching in vivo conditions. Both in human placenta and rat liver homogenates DNDGIC is formed spontaneously from GSH, S-nitroso-glutathione, and trace amounts of ferrous ions. DNDGIC is unstable in homogenates depleted of glutathione S-transferase (GST); an initial phase of rapid decomposition is followed by a slower decay, which is inversely proportional to the concentration. In the crude human placenta homogenate, GSTP1-1, which represents 90% of the cytosolic GST isoenzymes, is the preferential target for DNDGIC. It binds the complex almost stoichiometrically and stabilizes it for several hours (t1/2 = 8 h). In the presence of an excess of DNDGIC, negative cooperativity in GSTP1-1 opposes the complete loss of the usual detoxicating activity of this enzyme. In the rat liver homogenate, multiple endogenous GSTs (mainly Alpha and Mu class isoenzymes) bind the complex quantitatively and stabilize it (t1/2 = 4.5 h); negative cooperativity is also seen for these GSTs. Thus, the entire pool of cytosolic GSTs, with the exception of the Theta GST, represents a target for stoichiometric amounts of DNDGIC and may act as storage proteins for nitric oxide. These results confirm the existence of a cross-link between NO metabolism and the GST superfamily.
24-ott-2003
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
Animals; Glutathione; Humans; Glutathione Transferase; Feedback, Physiological; Ferrous Compounds; Protein Binding; Rats; Nitric Oxide; Glutathione S-Transferase pi; Rats, Sprague-Dawley; Half-Life; Placenta; Electron Spin Resonance Spectroscopy; Kinetics; Isoenzymes; Liver; Female
Turella, P., Pedersen, J.z., Caccuri, A.m., De Maria, F., Mastroberardino, P., LO BELLO, M., et al. (2003). Glutathione transferase superfamily behaves like storage proteins for dinitrosyl-diglutathionyl-iron complex in heterogeneous systems. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 278(43), 42294-42299 [10.1074/jbc.M305569200].
Turella, P; Pedersen, Jz; Caccuri, Am; De Maria, F; Mastroberardino, P; LO BELLO, M; Federici, G; Ricci, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/68654
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