Transient forebrain ischemia effects FAK-coupled signaling in gerbil hippocampus.
Focal adhesion kinase (FAK) is thought to play a major role in transducing extracellular matrix (ECM)-derived survival signals into cells. The function of FAK is linked to its autophosphorylation at Tyr-397 and then recruitment of several effector molecules. Thus, modulation of FAK activity may affect several intracellular signaling pathways and may participate in a variety of pathological settings. In the present study, we investigated the effect of short-term 5 min forebrain ischemia on levels and Tyr-397 phosphorylation of focal adhesion kinase and the interaction of this enzyme with Src protein tyrosine kinase and adapter protein p130Cas, involved in FAK-mediated signaling pathway in gerbil hippocampus. The total amount of focal adhesion kinase as well as its Tyr-397 phosphorylation declined substantially between 24 and 48 h after the insult, particularly in CA1 region of hippocampus. Concomitantly, a decreased amount of FAK/Src kinase complex has been observed. These data indicate that inhibition of FAK/Src-coupled signaling pathway may participate in the ischemia-induced neuronal degeneration in gerbil hippocampus. The temporal profile of FAK down-regulation in CA1 area coincides with metalloproteinases (MMPs) activation. These results suggest that extracellular proteolysis might belong to the mechanisms which govern the FAK-coupled pathway in ischemic hippocampus.
Ziemka-Nałecz
Małgorzata
M
NeuroRepair Department, Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland.
Zalewska
Teresa
T
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000201:enzymology* / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009410:Nerve Degeneration / Q000201:enzymology* / Q000503:physiopathology; D010766:Phosphorylation; D016548:Prosencephalon / Q000098:blood supply / Q000201:enzymology / Q000503:physiopathology; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D019061:src-Family Kinases / Q000378:metabolism
D050719:Crk-Associated Substrate Protein; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D020782:Matrix Metalloproteinases