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Pathological Conditions Involving Extracellular Hemoglobin: Molecular Mechanisms, Clinical Significance, and Novel Therapeutic Opportunities for alpha(1)-Microglobulin

Gram, Magnus LU ; Allhorn, Maria LU ; Bülow, Leif LU ; Hansson, Stefan LU ; Ley, David LU ; Olsson, Martin L LU ; Schmidtchen, Artur LU and Åkerström, Bo LU (2012) In Antioxidants & Redox Signaling 17(5). p.813-846
Abstract
Hemoglobin is the major oxygen-carrying system of the blood, but has many potentially dangerous side effects due to oxidation and reduction reactions of the heme-bound iron and oxygen. Extracellular hemoglobin, resulting from hemolysis or exogenous infusion, is shown to be an important pathogenic factor in a growing number of diseases. This review briefly outlines the oxidative/reductive toxic reactions of hemoglobin and its metabolites. It also describes physiological protection mechanisms that have evolved against extracellular hemoglobin, with a focus on the most recently discovered: the heme- and radical-binding protein α<sub>1</sub>-microglobulin (A1M). This protein is found in all vertebrates including man and operates by... (More)
Hemoglobin is the major oxygen-carrying system of the blood, but has many potentially dangerous side effects due to oxidation and reduction reactions of the heme-bound iron and oxygen. Extracellular hemoglobin, resulting from hemolysis or exogenous infusion, is shown to be an important pathogenic factor in a growing number of diseases. This review briefly outlines the oxidative/reductive toxic reactions of hemoglobin and its metabolites. It also describes physiological protection mechanisms that have evolved against extracellular hemoglobin, with a focus on the most recently discovered: the heme- and radical-binding protein α<sub>1</sub>-microglobulin (A1M). This protein is found in all vertebrates including man and operates by rapidly clearing cytosols and extravascular fluids of heme groups and free radicals released from hemoglobin. Five groups of pathological conditions with high concentrations of extracellular hemoglobin are described: hemolytic anemias and transfusion reactions, the pregnancy complication preeclampsia, cerebral intraventricular hemorrhage of premature infants, chronic inflammatory leg ulcers, and infusion of hemoglobin-based oxygen carriers as blood substitutes. Finally, possible treatments of these conditions are discussed, giving special attention to the described protective effects of A1M. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Antioxidants & Redox Signaling
volume
17
issue
5
pages
813 - 846
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000306082000010
  • pmid:22324321
  • scopus:84863487217
ISSN
1557-7716
DOI
10.1089/ars.2011.4282
language
English
LU publication?
yes
id
da237a23-b376-4a29-ac8d-2c8f469eaa82 (old id 2367042)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22324321?dopt=Abstract
date added to LUP
2012-03-02 10:55:00
date last changed
2017-10-22 04:19:19
@article{da237a23-b376-4a29-ac8d-2c8f469eaa82,
  abstract     = {Hemoglobin is the major oxygen-carrying system of the blood, but has many potentially dangerous side effects due to oxidation and reduction reactions of the heme-bound iron and oxygen. Extracellular hemoglobin, resulting from hemolysis or exogenous infusion, is shown to be an important pathogenic factor in a growing number of diseases. This review briefly outlines the oxidative/reductive toxic reactions of hemoglobin and its metabolites. It also describes physiological protection mechanisms that have evolved against extracellular hemoglobin, with a focus on the most recently discovered: the heme- and radical-binding protein α&lt;sub&gt;1&lt;/sub&gt;-microglobulin (A1M). This protein is found in all vertebrates including man and operates by rapidly clearing cytosols and extravascular fluids of heme groups and free radicals released from hemoglobin. Five groups of pathological conditions with high concentrations of extracellular hemoglobin are described: hemolytic anemias and transfusion reactions, the pregnancy complication preeclampsia, cerebral intraventricular hemorrhage of premature infants, chronic inflammatory leg ulcers, and infusion of hemoglobin-based oxygen carriers as blood substitutes. Finally, possible treatments of these conditions are discussed, giving special attention to the described protective effects of A1M.},
  author       = {Gram, Magnus and Allhorn, Maria and Bülow, Leif and Hansson, Stefan and Ley, David and Olsson, Martin L and Schmidtchen, Artur and Åkerström, Bo},
  issn         = {1557-7716},
  language     = {eng},
  number       = {5},
  pages        = {813--846},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Antioxidants & Redox Signaling},
  title        = {Pathological Conditions Involving Extracellular Hemoglobin: Molecular Mechanisms, Clinical Significance, and Novel Therapeutic Opportunities for alpha(1)-Microglobulin},
  url          = {http://dx.doi.org/10.1089/ars.2011.4282},
  volume       = {17},
  year         = {2012},
}