FK506 attenuates the post-ischemic perturbation of protein kinases and tyrosine phosphorylation in the gerbil hippocampal CA1 sectors

Abstract

To explore effects of Immunosuppressant FK506 on signal transduction pathway, we studied changes in subcellular distribution of protein kinase Cγ (PKCγ), CaM kinase II (CaMKII), as well as changes of tyrosine phosphorylation levels after ischemia. Male Mongolian gerbils were divided into 3 groups; FK506 (1 mg/kg, 3 mg/kg) and vehicle. FK506 was administered intravenously after 5 min ischemia. At the designated time points (0 time, 5 min ischemia, 1 hour, or 24 hour recovery), heads were frozen and samples were taken from CAl subfield of hippocampus. Western blot analysis was carried out with specific antibodies for PKCγ, CaMKII, and phosphotyrosine. FK506 administration significantly decreased translocation of PKCγ and CaMKII at 24 h of recovery (p < 0.05, ANOVA followed by Student-Newman Keuls' test) in P2 fraction. The levels of tyrosine phosphorylated pI60, pl40, plOO, p90, and pSO in P2 fraction were also significantly decreased with FK506 treatment at 24 h of recovery. The persistently elevated PKCγ and CaMKII level in P2 fraction which may be related to cell death, are attenuated with FK506 treatment. FK506 may contribute to recover calcium homeostasis in the post ischemic phase and promote cell survival. © Springer-Verlag 2003.