the chemical biology of HNO, is to determine the pharmacological and possible endogenous production of this species in vivo. One of the challenges is to determine the role that HNO may have in the biochemistry of nitric oxide synthase (NOS). In addition, we have found that NH2OH may be an important precursor to HNO under oxidative conditions. This indicates that hydroxyamic acids such as chemotherapeutic drugs hydroxyurea and SAHA may mediate some effects through HNO. Here we have investigated a variety of HNO donors and method of generation in vivo. We have currently discover a specific marker for HNO and found that it can be detected in cells. Furhtermore, we have been able to determine protemic and genomic signature that differ from HNO and NO. These finding furhter support our hypothesis that these species have mutaully exclusive biology.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011190-05
Application #
8763389
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2013
Total Cost
$67,074
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Paolocci, Nazareno; Wink, David A (2009) The shy Angeli and his elusive creature: the HNO route to vasodilation. Am J Physiol Heart Circ Physiol 296:H1217-20
Switzer, Christopher H; Flores-Santana, Wilmarie; Mancardi, Daniele et al. (2009) The emergence of nitroxyl (HNO) as a pharmacological agent. Biochim Biophys Acta 1787:835-40
Donzelli, Sonia; Espey, Michael Graham; Flores-Santana, Wilmarie et al. (2008) Generation of nitroxyl by heme protein-mediated peroxidation of hydroxylamine but not N-hydroxy-L-arginine. Free Radic Biol Med 45:578-84
Wink, David A; Paolocci, Nazareno (2008) Mother was right: eat your vegetables and do not spit! When oral nitrate helps with high blood pressure. Hypertension 51:617-9