FAK/Src family of kinases: protective or aggravating factor for ischemia reperfusion injury in nervous system?

• Published in: Expert opinion on therapeutic targets Vol. 19; no. 4; p. 539
• Main Authors: Bikis, Christos, Moris, Demetrios, Vasileiou, Ioanna, Patsouris, Eustratios, Theocharis, Stamatios
• Format: Journal Article
• Language: English
• Published: England 01.04.2015
• Subjects: Anesthetics - pharmacology; Animals; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Humans; Ischemic Preconditioning; Nervous System Diseases - physiopathology; Phosphorylation; Protein Kinase C - antagonists & inhibitors; Reperfusion Injury - physiopathology; src-Family Kinases - metabolism; Vascular Endothelial Growth Factor A - administration & dosage; ischemia-reperfusion injury; nervous system; Src; focal adhesion kinase
• ISSN: 1744-7631
• DOI: 10.1517/14728222.2014.990374

The focal adhesion kinase (FAK) and the Src families of kinases are subfamilies of the non-receptor protein tyrosine kinases. FAK activity is regulated by gene amplification, alternative splicing and phosporylation/dephosphorylation. FAK/Src complex has been found to participate through various pathways in neuronal models of ischemia-reperfusion injury (IRI) with conflicting results. The aim of the present review is to summarize the currently available data on this subject. The MEDLINE/PubMed database was searched for publications with the medical subject heading IRI and FAK and/or Src, nervous system. We restricted our search till 2014. We identified 93 articles that were available in English as abstracts or/and full-text articles that were deemed appropriate for our review. FAK has been found to have a beneficial preconditioning effect on IRI through activation via the protein kinase C (PKC) pathway by anesthetic agents. Of great importance are the interactions between FAK/Src and VEGF that has been already detected as a protective mean for IRI. The effect of VEGF administration might depend on dose as well as on time of administration. A Ca(2+)/calmodulin-dependent protein kinase II or PKC inhibitors seem to have protective effects on IRI by inhibiting ion channels activation.