Transient forebrain ischemia modulates signal transduction from extracellular matrix in gerbil hippocampus.
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.
Zalewska
Teresa
T
Laboratory of Molecular Neuropathology, Department of Neurochemistry, Medical Research Centre, Institute of Experimental and Clinical Medicine, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland. terezal@cmdik.pan.pl
Ziemka-Nalecz
Malgorzata
M
Sarnowska
Anna
A
Domańska-Janik
Krystyna
K
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005786:Gene Expression Regulation; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D016548:Prosencephalon; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015427:Reperfusion Injury / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
D007797:Laminin; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9