Document Detail


Hemoglobin-induced oxidative stress contributes to matrix metalloproteinase activation and blood-brain barrier dysfunction in vivo.
MedLine Citation:
PMID:  20354546     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hemoglobin (Hb) released from extravasated erythrocytes is implicated in brain edema after intracerebral hemorrhage (ICH). Hemoglobin is a major component of blood and a potent mediator of oxidative stress after ICH. Oxidative stress and matrix metalloproteinases (MMPs) are associated with blood-brain barrier (BBB) dysfunction. This study was designed to elucidate whether Hb-induced oxidative stress contributes to MMP-9 activation and BBB dysfunction in vivo. An intracerebral injection of Hb into rat striata induced increased hydroethidine (HEt) signals in parallel with MMP-9 levels. In situ gelatinolytic activity colocalized with oxidized HEt signals in vessel walls, accompanied by immunoglobulin G leakage and a decrease in immunoactivity of endothelial barrier antigen, a marker of endothelial integrity. Administration of a nonselective MMP inhibitor prevented MMP-9 levels and albumin leakage in injured striata. Moreover, reduction in oxidative stress by copper/zinc-superoxide dismutase (SOD1) overexpression reduced oxidative stress, MMP-9 levels, albumin leakage, and subsequent apoptosis compared with wild-type littermates. We speculate that Hb-induced oxidative stress may contribute to early BBB dysfunction and subsequent apoptosis, partly through MMP activation, and that SOD1 overexpression may reduce Hb-induced oxidative stress, BBB dysfunction, and apoptotic cell death.
Authors:
Masataka Katsu; Kuniyasu Niizuma; Hideyuki Yoshioka; Nobuya Okami; Hiroyuki Sakata; Pak H Chan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-31
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  30     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-01     Completed Date:  2010-12-20     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1939-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Albumins / metabolism
Animals
Apoptosis
Blood-Brain Barrier / drug effects*
Enzyme Activation
Hemoglobins / pharmacology*
Male
Matrix Metalloproteinase 2 / metabolism*
Matrix Metalloproteinase 9 / metabolism*
Oxidative Stress / drug effects*
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Superoxide Dismutase / metabolism
Grant Support
ID/Acronym/Agency:
P01 NS014543/NS/NINDS NIH HHS; P50 NS014543/NS/NINDS NIH HHS; P50 NS014543-29/NS/NINDS NIH HHS; R01 NS025372/NS/NINDS NIH HHS; R01 NS025372/NS/NINDS NIH HHS; R01 NS025372-21/NS/NINDS NIH HHS; R01 NS036147/NS/NINDS NIH HHS; R01 NS036147/NS/NINDS NIH HHS; R01 NS036147-14/NS/NINDS NIH HHS; R01 NS038653/NS/NINDS NIH HHS; R01 NS038653/NS/NINDS NIH HHS; R01 NS038653-12/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Albumins; 0/Hemoglobins; 0/Reactive Oxygen Species; EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.24/Mmp2 protein, rat; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

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


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