@article {2437,
	title = {Identification of Nitroxyl-induced Modifications in Human Platelet Proteins Using a Novel Mass Spectrometric Detection Method},
	journal = {Molecular \& Cellular Proteomics},
	volume = {8},
	number = {5},
	year = {2009},
	note = {ISI Document Delivery No.: 446JCTimes Cited: 5Cited Reference Count: 67Hoffman, Michael D. Walsh, Geraldine M. Rogalski, Jason C. Kast, Juergen},
	month = {May},
	pages = {887-903},
	type = {Article},
	abstract = {Nitroxyl (HNO) exhibits many important pharmacological effects, including inhibition of platelet aggregation, and the HNO donor Angeli{\textquoteright}s salt has been proposed as a potential therapeutic agent in the treatment of many diseases including heart failure and alcoholism. Despite this, little is known about the mechanism of action of HNO, and its effects are rarely linked to specific protein targets of HNO or to the actual chemical changes that proteins undergo when in contact with HNO. Here we study the presumed major molecular target of HNO within the body: protein thiols. Cysteine-containing tryptic peptides were reacted with HNO, generating the sulfinamide modification and, to a lesser extent, disulfide linkages with no other long lived intermediates or side products. The sulfinamide modification was subjected to a comprehensive tandem mass spectrometric analysis including MS/MS by CID and electron capture dissociation as well as an MS3 analysis. These studies revealed a characteristic neutral loss of HS(O)NH2 (65 Da) that is liberated from the modified cysteine upon CID and can be monitored by mass spectrometry. Upon storage, partial conversion of the sulfinamide to sulfinic acid was observed, leading to coinciding neutral losses of 65 and 66 Da (HS(O)OH). Validation of the method was conducted using a targeted study of nitroxylated glyceraldehyde-3-phosphate dehydrogenase extracted from Angeli{\textquoteright}s salt-treated human platelets. In these ex vivo experiments, the sample preparation process resulted in complete conversion of sulfinamide to sulfinic acid, making this the sole subject of further ex vivo studies. A global proteomics analysis to discover platelet proteins that carry nitroxyl-induced modifications and a mass spectrometric HNO dose-response analysis of the modified proteins were conducted to gain insight into the specificity and selectivity of this modification. These methods identified 10 proteins that are modified dose dependently in response to HNO, whose functions range from metabolism and cytoskeletal rearrangement to signal transduction, providing for the first time a possible mechanistic link between HNO-induced modification and the physiological effects of HNO donors in platelets. Molecular \& Cellular Proteomics 8: 887-903, 2009.},
	keywords = {ACTIVATION, ALDEHYDE, ALZHEIMERS-DISEASE, BIOLOGICAL-ACTIVITY, DEHYDROGENASE, DETERRENT AGENT CYANAMIDE, INTEGRIN, NITRIC-OXIDE, NITROGEN-OXIDE, NMDA RECEPTOR, S-NITROSYLATION, SUCCINIMIDE FORMATION},
	isbn = {1535-9476},
	url = {<Go to ISI>://000266116900002},
	author = {Hoffman, M. D. and Walsh, G. M. and Rogalski, J. C. and Kast, J.}
}
@article {4199,
	title = {Active oxygen species formation in synaptosomes exposed to an aluminum chelator},
	journal = {Neurotoxicology and Teratology},
	volume = {20},
	number = {3},
	year = {1998},
	note = {ISI Document Delivery No.: ZU241Times Cited: 4Cited Reference Count: 37},
	month = {May-Jun},
	pages = {317-320},
	type = {Article},
	abstract = {This study evaluates the potential of two chelators, 1,2-dimethyl-3-hydroxypyridine-4-one (Hdpp) and 1-n-butyl-2-methyl-3-hydroxypyridin-4-one (Hnbp), to modulate cerebral rates of free radical production. The fluorometric assay for 2{\textquoteright},7{\textquoteright}-dichlorofluorescein, which is formed by oxidation of a nonfluorescent precursor (2{\textquoteright},7{\textquoteright}-dichlorofluorescin diacetate), was used to assay reactive oxygen species (ROS) production. The chelator Hdpp alone and the aluminum complexes of each chelator, Al(dpp)(3) and Al(nbp)(3), all inhibited basal rates of generation of ROS within a rat cerebral synaptosomal fraction. In the presence of an iron salt (1 mu M FeSO4), a major enhancement of syn aptosomal ROS formation was apparent. However, with the addition of an equimolar concentration of Hdpp, Al(dpp)(3), or Al(nbp)(3), this stimulation was completely abolished. The N-substituted-3-hydroxy-4-pyridinones have been proposed to be of clinical utility for the removal of iron or aluminum from tissues. The clinical potential of this class of chelator may be enhanced by their ability to inhibit iron-related oxidative events. (C) 1998 Elsevier Science Inc.},
	keywords = {3-HYDROXY-4-PYRIDINONES, aluminum, ALZHEIMERS-DISEASE, CHELATOR, COMPLEXES, DEFEROXAMINE, DESFERRIOXAMINE, Free Radicals, hydroxypyridinones, iron, LIPID-PEROXIDATION, metal chelation, NEUROFIBRILLARY TANGLES, QUANTITATION, RATS, reactive oxygen species},
	isbn = {0892-0362},
	url = {<Go to ISI>://000074176500011},
	author = {Bondy, S. C. and Tseng, H. and Orvig, Chris}
}
@article {3692,
	title = {Speciation of aluminum in biological systems},
	journal = {Journal of Toxicology and Environmental Health},
	volume = {48},
	number = {6},
	year = {1996},
	note = {ISI Document Delivery No.: VE144Times Cited: 99Cited Reference Count: 131Research Issues in Aluminum Toxicity WorkshopJUL, 1995VANCOUVER, CANADA},
	month = {Aug},
	pages = {543-568},
	type = {Proceedings Paper},
	abstract = {As a {\textquoteright}{\textquoteright}hard{\textquoteright}{\textquoteright} trivalent metal ion, Al3+ binds strongly to oxygen-donor ligands such as citrate and phosphate. The aqueous coordination chemistry of Al is complicated by the tendency of many Al complexes to hydrolyze and form polynuclear species, many of which are sparingly soluble. Thus there is considerable variation among the Al stability constants reported for several important ligands. The complexity in the aqueous chemistry of Al has also affected Al toxicity studies, which have often utilized poorly characterized Al stock solutions. Serum fractionation studies show that most Al is protein bound, primarily to the serum iron transport protein transferrin. Albumin appears to play little, if any, role in serum transport. There is little agreement as to the speciation of the remaining low-molecular-mass fraction of serum Al. The lability of the Al3+ ion precludes the simple separation and identification of individual Al complexes. Computational methods are available for detailed computer calculations of the Al speciation in serum, but efforts in this area have been severely hampered by the uncertainties regarding the stability constants of the low molecular mass Al complexes with Citrate, phosphate, and hydroxide. Specific recommendations for further research on Al speciation include: (1) Determine more accurate Al stability constants with critical low molecular mass ligands such as citrate and phosphate; (2) supplement traditional potentiometric studies on Al complexes with data from other techniques such as Al-27-NMR and accelerator mass spectrometry with Al-26; (3) develop new methods for generating reliable linear free energy relationships for Al complexation; (4) determine equilibrium and rate constants for Al binding to transferrin al 37 degrees C; (5) confirm the possible formation of low-molecular-mass Al-protein complexes following desferrioxamine therapy; (6) continue research efforts to incorporate kinetic considerations into the present equilibrium speciation calculations; (7) improve methods for preparing chemically well-defined stock solutions for toxicological studies; (8) incorporate more detailed speciation data into studies on Al toxicity and pharmacokinetics; and (9) incorporate more detailed speciation data into future epidemiological studies on the relationship between Al toxicity and various water quality parameters.},
	keywords = {ALZHEIMERS-DISEASE, DIETARY CONSTITUENTS, DRINKING-WATER, GASTROINTESTINAL ABSORPTION, HUMAN-SERUM TRANSFERRIN, MURINE, NEUROBLASTOMA-CELLS, POTENTIAL, PROTEIN-BINDING, SIGNIFICANCE INVIVO, SIZE-EXCLUSION CHROMATOGRAPHY, THERAPEUTIC CHELATING-AGENTS},
	isbn = {0098-4108},
	url = {<Go to ISI>://A1996VE14400005},
	author = {Harris, W. R. and Berthon, G. and Day, J. P. and Exley, C. and Flaten, T. P. and Forbes, W. F. and Kiss, T. and Orvig, Chris and Zatta, P. F.}
}
