Biochemical characterization of S-nitrosohemoglobin. Mechanisms underlying synthesis, no release, and biological activity
Wolzt, Michael, MacAllister, Raymond J., Davis, Dana, Feelisch, Martin, Moncada, Salvador, Vallance, Patrick and Hobbs, Adrian J. (1999) Biochemical characterization of S-nitrosohemoglobin. Mechanisms underlying synthesis, no release, and biological activity. The Journal of Biological Chemistry, 274, (41), 28983-28990. (doi:10.1074/jbc.274.41.28983). (PMID:10506146).
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S-Nitrosohemoglobin (SNO-Hb) has been suggested to act as an endogenous NO donor and physiological regulator of blood pressure. However, the mechanisms responsible for the formation of SNO-Hb and those underlying the release of NO and subsequent biological activity have yet to be elucidated. In the present study, a number of nitrosated oxyhemoglobin (HbO(2)) derivatives have been synthesized and characterized. HbO(2) can be nitrosated at up to three distinct residues, one in the alpha-globin chain and two in the beta-chain. A beta-chain mononitrosated species (designated "SNO-Hb"), generated by the reaction of HbO(2) and S-nitrosoglutathione, released NO via a thiol-dependent mechanism involving nucleophilic attack at the nitrosated thiol functionality of SNO-Hb; in the case of glutathione, this process was associated with the formation of a mixed disulfide. In contrast, multinitrosated hemoglobin species released NO and relaxed vascular smooth muscle by a thiol-independent mechanism. HbO(2) scavenged potently NO released from SNO-Hb and inhibited its vasorelaxant properties. These data show that the predominant vasoactive species released from SNO-Hb is NO, with HNO a putative intermediate; the presence of a low molecular weight thiol is a prerequisite for this process. Such observations have important implications for the generation, metabolic fate, and biological activity of S-nitrosothiols.
|Digital Object Identifier (DOI):||doi:10.1074/jbc.274.41.28983|
|Subjects:||Q Science > QP Physiology
Q Science > QR Microbiology > QR180 Immunology
|Divisions:||Faculty of Medicine > Clinical and Experimental Sciences
|Date Deposited:||29 Jun 2012 11:06|
|Last Modified:||31 Mar 2016 14:27|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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