JNK acts as downstream effector of PLCγ in expression of hippocalcin

초록

Hippocalcin is a Ca2+ binding protein which is expressed mainly in the pyramidial nerve cell of the hippocampus. We have previously shown that bFGF induced hippocalcin expression, which leads to neurite outgrowth in H19-7 cells through the pathway of phospholipase γ (PLCγ). The expression of hippocalcin was increased by intracellular Ca2+, not by DAG. Hippocalcin overexpression also had critical effects on expressing Neuro D, a basic helix-loop-helix transcription factor. However, expression mechanism for hippocalcin still remains to be solved. There are some evidences that JNKs, also known as SAPKs, mediate neurogenesis in PC12-N1 and stem cell lines. To determine whether JNK signaling is involved in hippocalcin expression related with neurite outgrowth, H19-7 cells were treated with bFGF. The phosphorylation of JNK in H19-7 cells was increased at 5 min after the treatment with bFGF. To figure out this effect was due to PLCγ activation, H19-7 cells were pretreated with U73122, a PI-PLCγ inhibitor and Bapta-Am, a intracellular Ca2+ chelator for 30 min and 20min, respectively. The JNK activity was abolished significantly after both inhibitors treatment. To sum up, these data suggest that the phosphorylation of JNK has an important role in downstream of PLCγ in order to express hippocalcin in H19-7 cells.