TAILIEUCHUNG - Báo cáo khoa học: NO synthase isoforms specifically modify peroxynitrite reactivity

Nitric oxide synthases (NOSs) are multi-domain hemothiolate proteins that are the sole source of nitric oxide (NO) in mammals. NOSs can also be a source or a sink for peroxynitrite (PN), an oxidant that is suspected to be involved in numerous physiopathological processes. | ỊFEBS Journal NO synthase isoforms specifically modify peroxynitrite reactivity Amandine Maréchal1 Tony A. Mattioli1 Dennis J. Stuehr2 and Jerome Santolini1 1 Laboratoire Stress Oxydant et Detoxication iBiTec-S CEA Saclay Gif-sur-Yvette Cedex France 2 Department of Pathobiology Lerner Research Institute Cleveland Clinic Cleveland OH USA Keywords detoxification NO synthase oxidative stress peroxynitrite reactive nitrogen species Correspondence J. Santolini Laboratoire Stress Oxydant et Detoxication iBiTec-S and CNRS URA 2096 CEA Saclay 91191 Gif-sur-Yvette Cedex France Fax 33 1 69 08 87 17 Tel 33 1 69 08 53 63 E-mail Received 12 May 2010 revised 8 July 2010 accepted 22 July 2010 doi Nitric oxide synthases NOSs are multi-domain hemothiolate proteins that are the sole source of nitric oxide NO in mammals. NOSs can also be a source or a sink for peroxynitrite PN an oxidant that is suspected to be involved in numerous physiopathological processes. In a previous study we showed that the oxygenase domain of the inducible NOS iNOSoxy reacts with PN and changes its oxidative reactivity Marechal A Mattioli TA Stuehr DJ Santolini J 2007 J Biol Chem 282 14101-14112 . Here we report a similar analysis on two other NOS isoforms neuronal NOS nNOS and a bacterial NOS-like protein bsNOS . All NOSs accelerated PN decomposition with accumulation of a similar heme intermediate. The kinetics of PN decomposition and heme transitions were comparable among NOSs. However their effects on PN reactivity differ greatly. All isoforms suppressed PN two-electron oxidative activity but iNOSoxy enhanced PN one-electron oxidation and nitration potencies the oxygenase domain of nNOS nNOSoxy affected them minimally and bsNOS abolished all PN reactivities. This led to the loss of both NOS and PN decomposition activities for nNOSoxy and iNOSoxy which may be linked to the reported alterations in their electronic absorption spectra. Bacterial bsNOS

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