Linked Life Data

19493711

Source:http://linkedlifedata.com/resource/pubmed/id/19493711

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2009-9-23
pubmed:abstractText
Glutathionylated hemoglobin (Hb-SSG) is now recognized as a promising biomarker of systemic oxidative stress. Aim of this study is to gain a mechanistic insight into its formation. The ability of GSSG to form Hb-SSG through a thiol-disulfide exchange mechanism was firstly examined. For this purpose, GSSG (ranging from 0.23 to 230micromol/g Hb, 15microM-15mM final concentrations) was incubated with 1mM Hb and the relative content of Hb-SSG determined by direct infusion mass spectrometry (Orbitrap as analyzer). No detectable Hb-SSG was observed at a GSSG concentration range found in physiopathological conditions (0.13-0.23micromol/g Hb). To reach a detectable Hb-SSG signal, the GSSG concentration was raised to 2.3micromol/g Hb (0.5% relative abundance). The relative content of Hb-GSSG dose-dependently increased to 6% and 11% at 77 and 153micromol/g Hb, respectively. The second step was to demonstrate whether Hb-SSG is formed through a sulfenic acid intermediate, a well-recognized mechanism of S-protein glutathionylation. Cys beta93 sulfenic acid was found to be formed by oxidizing Hb with 1mM H(2)O(2), as demonstrated by direct infusion and LC-ESI-MS/MS experiments and using dimedone as derivatazing agent. When H(2)O(2)-treated Hb was incubated with physiological concentrations of GSH (9micromol/g Hb), the corresponding Hb-SSG form was detected, reaching 15% of relative abundance. In summary, we here demonstrate that Hb glutathionylation can occur through a Cys sulfenic acid intermediate which is formed in oxidizing conditions. Hb glutathionylation is also mediated by a thiol-disulfide transfer mechanism, but this requires a concentration of GSSG which is far to be achieved in physiopathological conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1873-376X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
877
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3456-61
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Hemoglobin glutathionylation can occur through cysteine sulfenic acid intermediate: electrospray ionization LTQ-Orbitrap hybrid mass spectrometry studies.
pubmed:affiliation
Dipartimento di Scienze Farmaceutiche Pietro Pratesi, Università degli Studi di Milano, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies