Transient forebrain ischemia modulates signal transduction from extracellular matrix in gerbil hippocampus

• Published in: Brain research 2003-07, Vol.977 (1), p.62-69
• Main Authors: Zalewska, Teresa, Ziemka-Nalęcz, Malgorzata, Sarnowska, Anna, Domańska-Janik, Krystyna
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel - methods; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases; Gene Expression Regulation; Gerbillinae; Hippocampus; Hippocampus - metabolism; Ischemic Attack, Transient - metabolism; Laminin; Laminin - metabolism; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Medical sciences; Meriones unguiculatus; Neurology; Prosencephalon; Protein-Tyrosine Kinases - metabolism; Reperfusion Injury - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Signal Transduction - physiology; Time Factors; Transient cerebral ischemia; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(03)02742-2

Cell adhesion to the extracellular matrix (ECM) functions as a survival factor and disruption of cell–ECM interaction can lead to cell death. Our previous study has demonstrated ischemia-induced enhancement of activity of extracellular metalloproteinases, which might result in the alteration of adhesive contact with ECM and affect the intracellular signaling pathway. The enzyme thought to play a major role in conveying survival signals from ECM to the cell interior is focal adhesion kinase (pp125 FAK). In the present study, the temporal relation between activation of extracellular metalloproteinases (MMP-2 and MMP-9), degradation of extracellular matrix protein laminin and the expression of pp125 FAK after 5 min of global ischemia in gerbil hippocampus were investigated. While significant activation of both investigated metalloproteinases occurred in the course of reperfusion, only changes in MMP-9 activity were correlated with degradation of laminin. These ischemia-induced extracellular events coincide temporarily with proteolytic modification of FAK protein and diminished level of its phosphorylated form, to about 50% of the initial value. These results are indicative of an involvement of ECM–pp125 FAK signaling pathway in ischemia-induced neuronal degeneration.