The novel compound TDN-345 induces synthesis/secretion of nerve growth factor in C6-10A glioma cells

Abstract

A novel compound, TDN-345, not bearing catechol moiety, induced NGF synthesis/secretion in C6-10A glioma cells. Both intracellular and extracellular nerve growth factor (NGF) protein levels increased within 3 h and reached a maximum around 12 h after the addition of TDN-345. The induction of NGF synthesis/secretion by TDN-345 occurred in a concentration-dependent manner, beginning with about 0.1 μM and reaching a maximum at 10 μM. The ED 50 was 0.88 μM. The induction was accompanied by an increase in NGF mRNA but not β-actin mRNA. In a time-course study, the NGF mRNA level was found to reach a maximum 2–3 h after the addition of TDN-345 and then to return to control levels. The induction occurred dose-dependently. The catecholaminergic compound epinephrine, which induces NGF synthesis/secretion, increased the intracellular cyclic AMP content by more than 1000-times at 10 μM. In contrast, TDN-345 did not cause such a prominent increase in cAMP even at 100 μM. These results indicate that TDN-345 induces NGF synthesis/secretion by increasing NGF mRNA expression, and the action of TDN-345 clearly differs from that of epinephrine, as it does not seem to involve cAMP as a second messenger. The results of the present study suggest the existence of a signal transduction pathway for NGF synthesis/secretion which is not mediated by cAMP.