BLOCKADE EFFECT OF NERVE GROWTH-FACTOR ON GM1 GANGLIOSIDE-INDUCED ACTIVATION OF TRANSGLUTAMINASE IN SUPERIOR CERVICAL SYMPATHETIC-GANGLIA EXCISED FROM ADULT-RAT

The activity of transglutaminase (TG), a Ca2+-dependent enzyme indicat ing tissue degradation or differentiation, showed in isolated adult ra t superior cervical ganglia (SCG) a rapid (within 15 to 30 min) and ma rked (approx. 5- to 8-fold) increase with the addition of either GM1 g anglioside (GM1, 5 nM), which is rich in synapses, or sialyl cholester ol (SC, 20 mu M), a synthetic sialic acid-containing compound, to the incubation medium at 37 degrees C. Under the same incubation condition s, addition of GM1 or SC decreased protein kinase C (PKC) activity (-2 6% to -39%) in the cytosolic fraction of the SCG, but increased the en zymic activity (+39% to +61%) in the particulate (cell membrane) fract ion, suggesting that a sialic acid-containing compound (GM1 or SC) pro motes PKC translocation from the cytosol to the membrane in ganglionic neurons. By contrast, addition of a promoting factor for survival of sympathetic neurons even in adulthood, nerve growth factor, (NGF, 0.25 mu g/ml) to the medium significantly decreased ganglionic TG activity (-43%). This inhibition was completely antagonized by the co-addition of NGF-monoclonal antibody (0.75 mu g/ml). An effective blockade of G M1- or SC-induced stimulation of ganglionic TG activity was seen by fu rther addition of NGF to the medium. Also, NGF almost abolished the tr anslocation of ganglionic PKC activity induced by the sialic acid-cont aining compounds, although either NGF or 12-O-tetradecanoylphorbol est er (TPA) alone stimulated the cytosolic PKC activity (approx. +30%) in the tissue. These findings imply that NGF may exert a blockade effect on GM1- or SC-evoked TG activation, possibly regulated by involvement of the PKC translocation process, as a result of alteration in the in tracellular Ca2+ environment.