Trapping of human hemoglobin by haptoglobin: Molecular mechanisms and clinical applications.
(2013) In Antioxidants & Redox Signaling 18(17). p.2364-2374- Abstract
- Significance: Haptoglobin (Hp) is an abundant plasma protein controlling the fate of hemoglobin (Hb) released from red blood cells after intravascular hemolysis. The complex formed between Hp and Hb is extraordinary strong, and once formed, this protein-protein association can be considered irreversible. Recent advances: A model of the Hp-Hb complex has been generated and the first steps towards understanding the mechanism behind the shielding effects of haptoglobin have been taken. The clinical potential of the complex for modulating inflammatory reactions and for functioning as an HBOC (hemoglobin-based oxygen carrier) have been described. Critical Issues: The three-dimensional structure of the Hp-Hb complex is unknown. Moreover, Hp is... (More)
- Significance: Haptoglobin (Hp) is an abundant plasma protein controlling the fate of hemoglobin (Hb) released from red blood cells after intravascular hemolysis. The complex formed between Hp and Hb is extraordinary strong, and once formed, this protein-protein association can be considered irreversible. Recent advances: A model of the Hp-Hb complex has been generated and the first steps towards understanding the mechanism behind the shielding effects of haptoglobin have been taken. The clinical potential of the complex for modulating inflammatory reactions and for functioning as an HBOC (hemoglobin-based oxygen carrier) have been described. Critical Issues: The three-dimensional structure of the Hp-Hb complex is unknown. Moreover, Hp is not a homogeneous protein. There are two common alleles at the Hp genetic locus denoted Hp1 and Hp2, which when analyzed on the protein levels result in differences between their physiological behavior, particularly in their shielding against hemoglobin-driven oxidative stress. Additional cysteine residues on the alpha-subunit allow Hp2 to form a variety of native multimers, which influence the biophysical and biological properties of Hp. The multimeric conformations in turn also modulate the glycosylation patterns of Hp by steric hindrance. Future Directions: A detailed analysis of the influence of Hp glycosylation will be instrumental to generate a deeper understanding of its biological function. Several pathological conditions also modify the glycan compositions allowing Hp to be potentially used as a marker protein for these disorders. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3047441
- author
- Ratanasopa, Khuanpiroon LU ; Chakane, Sandeep LU ; Nantasenamat, Chanin ; Ilyas, Muhammad and Bülow, Leif LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Antioxidants & Redox Signaling
- volume
- 18
- issue
- 17
- pages
- 2364 - 2374
- publisher
- Mary Ann Liebert, Inc.
- external identifiers
-
- wos:000318153400012
- pmid:22900934
- scopus:84876908109
- pmid:22900934
- ISSN
- 1557-7716
- DOI
- 10.1089/ars.2012.4878
- language
- English
- LU publication?
- yes
- id
- 48800b21-a4e4-4fcc-a7f1-2e6bdbd7c0cf (old id 3047441)
- date added to LUP
- 2016-04-01 11:04:23
- date last changed
- 2022-03-20 02:33:53
@article{48800b21-a4e4-4fcc-a7f1-2e6bdbd7c0cf,
abstract = {{Significance: Haptoglobin (Hp) is an abundant plasma protein controlling the fate of hemoglobin (Hb) released from red blood cells after intravascular hemolysis. The complex formed between Hp and Hb is extraordinary strong, and once formed, this protein-protein association can be considered irreversible. Recent advances: A model of the Hp-Hb complex has been generated and the first steps towards understanding the mechanism behind the shielding effects of haptoglobin have been taken. The clinical potential of the complex for modulating inflammatory reactions and for functioning as an HBOC (hemoglobin-based oxygen carrier) have been described. Critical Issues: The three-dimensional structure of the Hp-Hb complex is unknown. Moreover, Hp is not a homogeneous protein. There are two common alleles at the Hp genetic locus denoted Hp1 and Hp2, which when analyzed on the protein levels result in differences between their physiological behavior, particularly in their shielding against hemoglobin-driven oxidative stress. Additional cysteine residues on the alpha-subunit allow Hp2 to form a variety of native multimers, which influence the biophysical and biological properties of Hp. The multimeric conformations in turn also modulate the glycosylation patterns of Hp by steric hindrance. Future Directions: A detailed analysis of the influence of Hp glycosylation will be instrumental to generate a deeper understanding of its biological function. Several pathological conditions also modify the glycan compositions allowing Hp to be potentially used as a marker protein for these disorders.}},
author = {{Ratanasopa, Khuanpiroon and Chakane, Sandeep and Nantasenamat, Chanin and Ilyas, Muhammad and Bülow, Leif}},
issn = {{1557-7716}},
language = {{eng}},
number = {{17}},
pages = {{2364--2374}},
publisher = {{Mary Ann Liebert, Inc.}},
series = {{Antioxidants & Redox Signaling}},
title = {{Trapping of human hemoglobin by haptoglobin: Molecular mechanisms and clinical applications.}},
url = {{http://dx.doi.org/10.1089/ars.2012.4878}},
doi = {{10.1089/ars.2012.4878}},
volume = {{18}},
year = {{2013}},
}