Linked Life Data

20568812

Source:http://linkedlifedata.com/resource/pubmed/id/20568812

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-8-6
pubmed:abstractText
The reaction of hemoglobin (Hb) with hydrogen peroxide (H(2)O(2)) results in free radicals generated at the heme iron, followed by radical transfer to the porphyrin/globin. In the present work, we employed isobaric tagging for relative and absolute quantification (iTRAQ) and a LC-MALDI-MS/MS-based proteomic approach to identify the extent of oxidative changes within tetrameric Hb and dimeric Hb-haptoglobin (Hb-Hp) complexes. Extensive oxidative modifications were found to be restricted to peptides containing alphaTyr42, betaTyr145, and betaCys93. The protein region composed of these peptides appears to define an area of oxidative activity within the Hb tetramer that extends across the critical alpha1beta2/alpha2beta1 interface. Extensive oxidative modifications occurring at betaCys93 indicate that this surface amino acid is an important end point for free radical induced protein oxidation within Hb. Conversely when Hp 1-1 or 2-2 was complexed with dissociable Hb, oxidative changes in Hp complexed dimeric Hb were prevented. This protection was not observed in a stabilized tetrameric Hb, which displays a weak binding affinity for Hp. Therefore, dimerization of Hb and Hp binding may interfere with free radical translocation and play an important role in the overall antioxidant mechanism of Hp. Interestingly, the prevention of peroxide induced Hb amino acid oxidation in purified Hb-Hp1-1 and Hb-Hp2-2 was found to be equal, indicating a phenotype independent specificity in the process of oxidative protection. Taken together, these data suggest differences in oxidative modifications resulting from peroxide induced heme emanated free radical distribution in tetrameric compared to Hp1-1/Hp2-2 stabilized dimeric Hb.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1535-3907
pubmed:author
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4061-70
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Quantitative mass spectrometry defines an oxidative hotspot in hemoglobin that is specifically protected by haptoglobin.
pubmed:affiliation
Department of Chemistry and Applied Biosciences, ETH Zurich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't