Effect of substance P and protein kinase inhibitors on beta-amyloid peptide-induced proliferation of cultured brain cells.
The present study investigated the effect of substance P (SP) and protein kinase inhibitors (H7 and HA1004) on beta-amyloid peptide-induced proliferation of neonatal rat brain cells in primary cultures. The beta-amyloid peptide1-28 (designated as beta AP28), at nanomolar concentrations (10(-9) M), significantly (P < or = 0.05) increased the proliferation of brain cells (presumably non-neuronal) as measured by [3H]thymidine uptake into DNA (mitogenesis). The effect was dependent on time of culture, concentration of beta AP28, and presence of fetal calf serum. The supplementation of SP into cell cultures at time zero reversed the proliferative response of beta AP28. Moreover, the beta AP28-induced proliferation was inhibited by protein kinase inhibitor H7, but not by HA1004. Since H7 is a selective protein kinase C (PKC) inhibitor and SP action involves PKC, we conclude that beta AP28 induces normal brain cell proliferation through PKC pathway of cell signaling.
Singh
V K
VK
Department of Biology, Utah State University, Logan 84322-6800.
Cheng
J F
JF
Leu
S J
SJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology*; D013449:Sulfonamides; D013936:Thymidine / Q000378:metabolism
D016229:Amyloid beta-Peptides; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D013373:Substance P; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D013936:Thymidine