Linked Life Data

18729428

Source:http://linkedlifedata.com/resource/pubmed/id/18729428

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
2008-9-11
pubmed:abstractText
Cyclic nitroxides effectively protect cells, tissues, isolated organs, and laboratory animals from radical-induced damage. The present study focuses on the kinetics and mechanisms of the reactions of piperidine and pyrrolidine nitroxides with thiyl radicals, which are involved in free radical "repair" equilibria, but being strong oxidants can also produce cell damage. Thiyl radicals derived from glutathione, cysteine, and penicillamine were generated in water by pulse radiolysis, and the rate constants of their reactions with 2,2,6,6-tetramethylpiperidine-1-oxyl (TPO), 4-OH-TPO, and 3-carbamoyl-proxyl were determined to be (5-7) x 10 (8) M (-1) s (-1) at pH 5-7, independent of the structure of the nitroxide and the thiyl radical. It is suggested that the reaction of nitroxide (>NO (*)) with thiyl radical (RS (*)) yields an unstable adduct (>NOSR). The deprotonated form of this adduct decomposes via heterolysis of the N-O bond, yielding the respective amine (>NH) and sulfinic acid (RS(O)OH). The protonated form of the adduct decomposes via homolysis of the N-O bond, forming the aminium radical (>NH (*+)) and sulfinyl radical (RSO (*)), which by subsequent reactions involving thiol and nitroxide produce the respective amine and sulfonic acid (RS(O) 2OH). Nitroxides that are oxidized to the respective oxoammonium cations (>N (+)O) are recovered in the presence of NADH but not in the presence of thiols. This suggests that the reaction of >N (+)O with thiols yields the respective amine. Two alternative mechanisms are suggested, where >N (+)O reacts with thiolate (RS (-)) directly generating the adduct >NOSR or indirectly forming >NO (*) and RS (*), which subsequently together yield the adduct >NOSR. Under physiological conditions the adduct is mainly deprotonated, and therefore nitroxides can detoxify thiyl radicals. The proposed mechanism can account for the protective effect of nitroxides against reactive oxygen- and nitrogen-derived species in the presence of thiols.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-5215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8600-5
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Kinetics of the reaction between nitroxide and thiyl radicals: nitroxides as antioxidants in the presence of thiols.
pubmed:affiliation
Institute of Chemistry and the Accelerator Laboratory, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. sarag@vms.huji.ac.il
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't