Document Detail


Hemopexin decreases hemin accumulation and catabolism by neural cells.
MedLine Citation:
PMID:  22342655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hemopexin is a serum, CSF, and neuronal protein that is protective after experimental stroke. Its efficacy in the latter has been linked to increased expression and activity of heme oxygenase (HO)-1, suggesting that it facilitates heme degradation and subsequent release of cytoprotective biliverdin and carbon monoxide. In this study, the effect of hemopexin on the rate of hemin breakdown by CNS cells was investigated in established in vitro models. Equimolar hemopexin decreased hemin breakdown, as assessed by gas chromatography, by 60-75% in primary cultures of murine neurons and glia. Extracellular hemopexin reduced cell accumulation of ⁵⁵Fe-hemin by over 90%, while increasing hemin export or extraction from membranes by fourfold. This was associated with significant reduction in HO-1 expression and neuroprotection. In a cell-free system, hemin breakdown by recombinant HO-1 was reduced over 80% by hemopexin; in contrast, albumin and two other heme-binding proteins had no effect. Although hemopexin was detected on immunoblots of cortical lysates from adult mice, hemopexin knockout per se did not alter HO activity in cortical cells treated with hemin. These results demonstrate that hemopexin decreases the accumulation and catabolism of exogenous hemin by neural cells. Its beneficial effect in stroke models is unlikely to be mediated by increased production of cytoprotective heme breakdown products.
Authors:
Jing Chen-Roetling; Wenpei Liu; Raymond F Regan
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-07
Journal Detail:
Title:  Neurochemistry international     Volume:  60     ISSN:  1872-9754     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  2012-07-23     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  488-94     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Chromatography, Gas
Enzyme Induction
Heme Oxygenase-1 / biosynthesis,  metabolism
Hemin / metabolism*
Hemopexin / genetics,  physiology*
Mice
Mice, Knockout
Neurons / metabolism*
Grant Support
ID/Acronym/Agency:
NS42273/NS/NINDS NIH HHS; NS74289/NS/NINDS NIH HHS; R01 NS042273/NS/NINDS NIH HHS; R01 NS042273-08/NS/NINDS NIH HHS; R21 NS074289/NS/NINDS NIH HHS; R21 NS074289-01A1/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
743LRP9S7N/Hemin; 9013-71-2/Hemopexin; EC 1.14.99.3/Heme Oxygenase-1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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