FK506 ANTAGONIZES APOPTOSIS AND C-JUN PROTEIN EXPRESSION IN NEURONAL CULTURES

FK506 is an immunosuppressive drug that binds to FK506 binding protein (FKBPs), a subgroup of cytosolic proteins called immunophillins. Prev ious works have revealed that FK506 protects neural cells from ischemi a or excitotoxicity. Here we report that FK506 (10(-6) M) and not cycl osporine A (10(-6) M) blocks neuronal apoptosis induced by serum depri vation in rat neuronal cultures. In addition the immunohistochemical s taining of C-jun protein in deprived cultures is markedly attenuated b y FK506. The proportion of C-jun-positive neurons in control cultures, in serum-deprived cultures (48 h) and in serum-deprived cultures expo sed to FK506 (10(-6) M) were 12.5%, 56.5% and 16.5%, respectively. The down-regulation of C-jun could play a major role in the anti-apoptoti c action of FK506 in stressed neuronal cultures. (C) 1998 Rapid Scienc e Ltd.