Effect of substance P and protein kinase inhibitors on β-amyloid peptide-induced proliferation of cultured brain cells

doi:10.1016/0006-8993(94)91313-7

Brain Research

Volume 660, Issue 2, 17 October 1994, Pages 353-356

https://doi.org/10.1016/0006-8993(94)91313-7 Get rights and content

Abstract

The present study investigated the effect of substance P (SP) and protein kinase inhibitors (H7 and HA1004) on β-amyloid peptide-induced proliferation of neonatal rat brain cells in primary cultures. The β-amyloid peptide_1–28 (designated as βAP28), at nanomolar concentrations (10⁻⁹ M), significantly (P ⪯ 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 cultured, concentration of βAP28, and presence of fetal calf serum. The supplementation of SP into cell cultures at time zero reversed the proliferative response of βAP28. Moreover, the βAP28-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 βAP28 induces normal brain cell proliferation through PKC pathway of cell signaling.

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^☆: This research was supported by a grant from the Biotechnology Center, Utah State University, Logan, UT.

^∗∗: The two graduate students (J.F.C. and S.Y.L.) thank the Utah State University's Gradaute Program in Molecular Biology for partial support of their tution fee.

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Short communicationEffect of substance P and protein kinase inhibitors on β-amyloid peptide-induced proliferation of cultured brain cells☆

Abstract

Brain Res.

Biochem. Biophys. Res. Commun.

Meth. Enzymol.

Brain Res.

J. Neuroimmunol.

Neurosci. Lett.

Amyloid β-protein activates tachykinin receptors and inositol triphosphate accumulation by synergy with glutamate

Soluble β-amyloid induction of Alzheimer's phenotype for human fibroblast K+ channels

Science

Amyloid β-peptide is produced by cultured cells during normal metabolism

Nature

Amyloid β-protein deposition in tissues other than brain in Alzheimer's disease

Nature

Generation of β-amyloid in the secretory pathway in neuronal and nonneuronal cells

Short communication
Effect of substance P and protein kinase inhibitors on β-amyloid peptide-induced proliferation of cultured brain cells☆