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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-35669

Pimenova, T; Pereira, C P; Gehrig, P; Buehler, P W; Schaer, D J; Zenobi, R (2010). Quantitative mass spectrometry defines an oxidative hotspot in hemoglobin that is specifically protected by haptoglobin. Journal of Proteome Research, 9(8):4061-4070.

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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.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
04 Faculty of Medicine > Functional Genomics Center Zurich
08 University Research Priority Programs > Systems Biology / Functional Genomics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:20 Sep 2010 11:56
Last Modified:05 Apr 2016 14:14
Publisher:American Chemical Society
Publisher DOI:10.1021/pr100252e
PubMed ID:20568812

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