RGD Reference Report - Role of matrix metalloproteinases in apoptosis after transient focal cerebral ischemia in rats and mice. - Rat Genome Database

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Role of matrix metalloproteinases in apoptosis after transient focal cerebral ischemia in rats and mice.

Authors: Copin, JC  Goodyear, MC  Gidday, JM  Shah, AR  Gascon, E  Dayer, A  Morel, DM  Gasche, Y 
Citation: Copin JC, etal., Eur J Neurosci. 2005 Oct;22(7):1597-608.
RGD ID: 8547921
Pubmed: PMID:16197500   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1460-9568.2005.04367.x   (Journal Full-text)

The involvement of matrix metalloproteinases (MMPs) in cerebral ischemia-induced apoptosis was investigated in a model of transient focal cerebral ischemia in rats treated intracerebroventricularly (i.c.v.) with 4-((3-(4-phenoxylphenoxy)propylsulfonyl)methyl)-tetrahydropyran-4-carboxylic acid N-hydroxy amide, a broad spectrum non-peptidic hydroxamic acid MMP inhibitor, and in MMP-9-deficient mice. Our results showed that MMP inhibition reduced DNA fragmentation by 51% (P < 0.001) and cerebral infarct by 60% (P < 0.05) after ischemia. This protection was concomitant with a 29% reduction of cytochrome c release into the cytosol (P < 0.005) and a 54% reduction of calpain-related alpha-spectrin degradation (P < 0.05), as well as with an 84% increase in the immunoreactive signal of the native form of poly(ADP) ribose polymerase (P < 0.01). By contrast, specific targeting of the mmp9 gene in mice did reduce cerebral damage by 34% (P < 0.05) but did not modify the apoptotic response after cerebral ischemia. However, i.c.v. injection of MMP-9-deficient mice with the same broad-spectrum inhibitor used in rats significantly reduced DNA degradation by 32% (P < 0.05) and contributed even further to the protection of the ischemic brain. Together, our pharmacological and genetic results indicate that MMPs other than MMP-9 are actively involved in cerebral ischemia-induced apoptosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia  ISOMmp9 (Mus musculus)8547921; 8547921 RGD 
transient cerebral ischemia  IMP 8547921 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information