A novel role for hippocalcin in bFGF-induced neurite outgrowth of H19-7 cells

초록

Hippocalcin is a Ca2+ binding protein which is expressed mainly in the pyramidal nerve cell of the hippocampus, but the mechanism and functions underlying hippocalcin in the brain remains unclear. To elucidate a role of hippocalcin, we utilized a conditionally immortalized hippocampal cell line (H19-7). We show here that bFGF-induced hippocalcin expression is involved in neurite outgrowth of H19-7 cells. Increased expression of hippocalcin dramatically elongated neurites induced by bFGF stimulation and was concurrent with the expression of basic helix-loop-helix (bHLH) transcription factor, NeuroD. Hippocalcin suppression blocked bFGF-induced neurite outgrowth and NeuroD expression. Stimulation of bFGF resulted in the activation of phospholipase C- (PLC- ) and Ca2+. Hippocalcin expression by bFGF stimulation was fully blocked by both the PLC- inhibitor, U73122 and a chelator of intracellular Ca2+, BAPTA-AM, suggesting that hippocalcin expression by bFGF stimulation is dependent on PLC- and Ca2+. Moreover, both U73122 and BAPTA-AM completely blocked bFGF-induced neurite outgrowth and NeuroD expression. Taken together, these results suggest for the first time that bFGF induces hippocalcin expression through PLC- activation and Ca2+, which leads to neurite outgrowth in H19-7 cells.