TY - JOUR
T1 - Involvement of Protein Kinase C in Ca2+‐Signaling Pathways to Activation of AP‐1 DNA‐Binding Activity Evoked via NMDA‐ and Voltage‐Gated Ca2+ Channels
AU - Ohtani, Ken‐ichi ‐i
AU - Sakurai, Hiroaki
AU - Oh, Esther
AU - Iwata, Emi
AU - Tsuchiya, Tomofusa
AU - Tsuda, Masaaki
PY - 1995/8
Y1 - 1995/8
N2 - Abstract: Stimulation of cultured cerebellar granule cells with N‐methyl‐d‐aspartate (NMDA) or kainic acid (KA) leads to activation of activator protein‐1 (AP‐1) DNA‐binding activity, which can be monitored by an increase in 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐responsive element (TRE)‐binding activity, in concert with c‐fos induction. For this increase in TRE‐binding activity, Ca2+ influx across the plasma membrane is essential. Treatment of cells with an intracellular Ca2+ chelator, BAPTA‐AM, abolished this increase. Close correspondence between the dose‐response curves of 45Ca2+ uptake and TRE‐binding activity by NMDA or KA suggested that Ca2+ influx not only triggered sequential activation of Ca2+‐signaling processes leading to the increase in TRE‐binding activity, but also controlled its increased level. Stimulation of non‐NMDA receptors by KA mainly caused Ca2+ influx through voltage‐gated Ca2+ channels, whereas stimulation of NMDA receptors caused Ca2+ influx through NMDA‐gated ion channels. The protein kinase C (PKC) inhibitors staurosporine and calphostin C inhibited the increase in TRE‐binding activity caused by NMDA and KA at the same concentration at which they inhibited that caused by TPA. Furthermore, down‐regulation of PKC inhibited the increase in TRE‐binding activity by NMDA and KA. Thus, a common pathway that includes PKC could, at least in part, be involved in the Ca2+‐signaling pathways for the increase in TRE‐binding activity coupled with the activation of NMDA‐ and non‐NMDA receptors.
AB - Abstract: Stimulation of cultured cerebellar granule cells with N‐methyl‐d‐aspartate (NMDA) or kainic acid (KA) leads to activation of activator protein‐1 (AP‐1) DNA‐binding activity, which can be monitored by an increase in 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐responsive element (TRE)‐binding activity, in concert with c‐fos induction. For this increase in TRE‐binding activity, Ca2+ influx across the plasma membrane is essential. Treatment of cells with an intracellular Ca2+ chelator, BAPTA‐AM, abolished this increase. Close correspondence between the dose‐response curves of 45Ca2+ uptake and TRE‐binding activity by NMDA or KA suggested that Ca2+ influx not only triggered sequential activation of Ca2+‐signaling processes leading to the increase in TRE‐binding activity, but also controlled its increased level. Stimulation of non‐NMDA receptors by KA mainly caused Ca2+ influx through voltage‐gated Ca2+ channels, whereas stimulation of NMDA receptors caused Ca2+ influx through NMDA‐gated ion channels. The protein kinase C (PKC) inhibitors staurosporine and calphostin C inhibited the increase in TRE‐binding activity caused by NMDA and KA at the same concentration at which they inhibited that caused by TPA. Furthermore, down‐regulation of PKC inhibited the increase in TRE‐binding activity by NMDA and KA. Thus, a common pathway that includes PKC could, at least in part, be involved in the Ca2+‐signaling pathways for the increase in TRE‐binding activity coupled with the activation of NMDA‐ and non‐NMDA receptors.
KW - AP‐1
KW - Ca influx
KW - Cerebellar granule cells
KW - Glutamate receptors
KW - Protein kinase C
KW - c‐fos induction
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U2 - 10.1046/j.1471-4159.1995.65020605.x
DO - 10.1046/j.1471-4159.1995.65020605.x
M3 - Article
C2 - 7616215
AN - SCOPUS:0029144614
VL - 65
SP - 605
EP - 614
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -