Quantitative Mass Spectrometry Defines an Oxidative Hotspot in Hemoglobin that is Specifically Protected by Haptoglobin

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Author(s) Pimenova, Tatiana, Pereira, Claudia P., Gehrig, Peter, Buehler, Paul W., Schaer, Dominik J., Zenobi, Renato
Publication Type Journal Items, Publication Status: Published
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Title Quantitative Mass Spectrometry Defines an Oxidative Hotspot in Hemoglobin that is Specifically Protected by Haptoglobin
Author(s) Pimenova, Tatiana
Pereira, Claudia P.
Gehrig, Peter
Buehler, Paul W.
Schaer, Dominik J.
Zenobi, Renato
Journal or Series Title Journal of proteome research
Volume Number 9
Issue Number 8
Start Page 4061
End Page 4070
ISSN 1535-3893
1535-3907
Publisher American Chemical Society
Publication Place Washington, DC
Publication Date 2010
Keyword(s) hemoglobin oxidation
haptoglobin
quantification
iTRAQ
mass spectrometry
Abstract The reaction of hemoglobin (Hb) with hydrogen peroxide (H2O2) 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 alpha Tyr42, beta Tyr145, and beta Cys93. The protein region composed of these peptides appears to define an area of oxidative activity within the Hb tetramer that extends across the critical alpha 1 beta 2/alpha 2 beta 1 interface. Extensive oxidative modifications occurring at beta Cys93 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.
DOI 10.1021/pr100252e
Additional Notes Received March 19 2010, Published online June 22 2010
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 02207
03430
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NEBIS System Number 004296166
Source Database ID WOS-000280583700028
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@article{Pmnv2010,
  author = "Pimenova, Tatiana and Pereira, Claudia P. and Gehrig, Peter and Buehler, Paul W. and Schaer, Dominik J. and Zenobi, Renato",
  title = "{Q}uantitative {M}ass {S}pectrometry {D}efines an {O}xidative {H}otspot in {H}emoglobin that is {S}pecifically {P}rotected by {H}aptoglobin",
  journal = "Journal of proteome research",
  year = 2010,
  volume = "9",
  number = "8",
  pages = "4061--4070",
}


E-Citations record created: Mon, 06 Sep 2010, 08:13:22 CET