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Role of Ca 2+ in Differentiation Mediated by Nerve Growth Factor and Dibutyryl Cyclic AMP in PC12 Cells
Author(s) -
Huang ChunMing,
Tsay KunEng,
Kao LungSen
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67020530.x
Subject(s) - neurite , nerve growth factor , intracellular , extracellular , microbiology and biotechnology , bucladesine , thapsigargin , biology , cellular differentiation , medicine , chemistry , endocrinology , in vitro , biochemistry , receptor , gene
Nerve growth factor (NGF) and dibutyryl cyclic AMP (dbcAMP) have synergistic effects on the neurite outgrowth of rat pheochromocytoma PC12 cells. The sites of interaction between NGF and dbcAMP have been studied extensively; however, the role of Ca 2+ in differentiation induced by the two agents remains unclear. To understand whether intracellular Ca 2+ is involved in the differentiation induced by the two agents, PC12 cells were treated with NGF, dbcAMP, or NGF plus dbcAMP for 2 days, and then effects on neurite outgrowth, ATP‐induced Ca 2+ influx, and Ca 2+ mobilization from intracellular Ca 2+ pools were examined. NGF or dbcAMP alone enhanced neurite outgrowth and Ca 2+ accumulation by nonmitochondrial Ca 2+ pools or the thapsigargin (TG)‐sensitive Ca 2+ pool. The dbcAMP acted synergistically with NGF to increase neurite outgrowth and to enlarge the TG‐sensitive Ca 2+ pool. The synergistic effect occurred within the first hour of treatment with dbcAMP plus NGF. On the other hand, dbcAMP abolished NGF's ability to enhance ATP‐induced influx of extracellular Ca 2+ . Therefore, NGF and dbcAMP induced different effects on Ca 2+ signaling pathways through two different but interacting pathways. In PC12 cells pretreated with TG to deplete the TG‐sensitive Ca 2+ pool, the dbcAMP‐ or dbcAMP plus NGF‐mediated neurite outgrowth was significantly inhibited, whereas NGF‐mediated neurite outgrowth was not affected by TG pretreatment. Our results suggest that the intracellular nonmitochondrial Ca 2+ pools were changed in the differentiation process and were necessary for the synergistic effect of NGF and dbcAMP.