TY - JOUR
T1 - Involvement of endogenous PACAP expression in the activity-dependent survival of mouse cerebellar granule cells
AU - Tabuchi, Akiko
AU - Koizumi, Motoko
AU - Nakatsubo, Jun
AU - Yaguchi, Takahiro
AU - Tsuda, Masaaki
N1 - Funding Information:
We thank Dr I. Shibuya (University of Occupational and Environmental Health, School of Medicine, Japan) for helpful discussion. This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, and by a Grant-in-Aid for the Core Research for Evolutional Science and Technology (CREST) from the Science and Technology Corporation of Japan.
PY - 2001
Y1 - 2001
N2 - Membrane depolarization causes Ca2+ influx through L-type voltage-dependent calcium channels (L-VDCC), which promotes the activity-dependent survival of mouse cerebellar granule cells (CGCs). Although exogenously added pituitary adenylate cyclase activating polypeptide (PACAP) is effective in promoting the survival of CGCs, it is unknown whether PACAP is synthesized in CGCs and involved in the activity-dependent survival of CGCs. In this study, we found that the PACAP gene was activated in depolarized CGCs cultured at 25 mM KCl (high K+), independently of de novo protein synthesis. In addition, the PACAP immunoreactivity increased through the activation of L-VDCC in depolarized CGCs, indicating that PACAP is concomitantly produced with PACAP mRNA in an activity-dependent manner. Exogenously added PACAP attenuated the apoptosis of CGCs through a specific interaction with PACAP receptors. Furthermore, a PACAP receptor antagonist, PACAP(6-38), reduced the survival of CGCs at high K+. These findings indicate that endogenous PACAP production induced by Ca2+ signals exerts a survival effect on CGCs via PACAP receptors, which, at least in part, accounts for the activity-dependent survival of CGCs.
AB - Membrane depolarization causes Ca2+ influx through L-type voltage-dependent calcium channels (L-VDCC), which promotes the activity-dependent survival of mouse cerebellar granule cells (CGCs). Although exogenously added pituitary adenylate cyclase activating polypeptide (PACAP) is effective in promoting the survival of CGCs, it is unknown whether PACAP is synthesized in CGCs and involved in the activity-dependent survival of CGCs. In this study, we found that the PACAP gene was activated in depolarized CGCs cultured at 25 mM KCl (high K+), independently of de novo protein synthesis. In addition, the PACAP immunoreactivity increased through the activation of L-VDCC in depolarized CGCs, indicating that PACAP is concomitantly produced with PACAP mRNA in an activity-dependent manner. Exogenously added PACAP attenuated the apoptosis of CGCs through a specific interaction with PACAP receptors. Furthermore, a PACAP receptor antagonist, PACAP(6-38), reduced the survival of CGCs at high K+. These findings indicate that endogenous PACAP production induced by Ca2+ signals exerts a survival effect on CGCs via PACAP receptors, which, at least in part, accounts for the activity-dependent survival of CGCs.
KW - Apoptosis
KW - Ca channel
KW - Calcium
KW - Cell survival
KW - Cerebellar granule cells
KW - Gene expression
KW - PACAP
UR - http://www.scopus.com/inward/record.url?scp=0035163010&partnerID=8YFLogxK
U2 - 10.1016/S0168-0102(00)00200-5
DO - 10.1016/S0168-0102(00)00200-5
M3 - 学術論文
C2 - 11164256
AN - SCOPUS:0035163010
SN - 0168-0102
VL - 39
SP - 85
EP - 93
JO - Neuroscience Research
JF - Neuroscience Research
IS - 1
ER -