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

To explore effects of immunosuppressant FK506 on signal transduction pathway, we studied changes in subcellular distribution of protein kinase Cgamma (PKCgamma), CaM kinase 11 (CaMKII), as well as changes of tyrosine phosphorylation levels after ischemia. Male Mongolian gerbils were divided into three groups; FK506 (1 and 3 mg/kg) and vehicle. FK506 was administered intravenously after 5 min ischemia. At the designated time points (0 time, 5 min ischemia, 1 or 24 h recovery), heads were frozen and samples were taken from CA1 subfield of hippocampus. Western blot analysis was carried out with specific antibodies for PKCgamma, CaMKII, and phosphotyrosine. FK506 administration significantly decreased translocation of PKCgamma 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 p160, p140, p100, p90, and p80 in P2 fraction were decreased with FK506 treatment at 24 h of recovery. The persistently elevated PKCgamma 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 post ischemic phase and promote cell survival. (C) 2003 Elsevier Science B.V. All rights reserved.