RRC ID 33957
Author Satoh T, Furuta K, Tomokiyo K, Nakatsuka D, Tanikawa M, Nakanishi M, Miura M, Tanaka S, Koike T, Hatanaka H, Ikuta K, Suzuki M, Watanabe Y.
Title Facilitatory roles of novel compounds designed from cyclopentenone prostaglandins on neurite outgrowth-promoting activities of nerve growth factor.
Journal J Neurochem
Abstract Cyclopentenone prostaglandins (PGs) are known to arrest the cell cycle at the G(1) phase in vitro and to suppress tumor growth in vivo. However, their effects on neurons are unclear. Here, we report that some cyclopentenone PGs function as neurite outgrowth-promoting factors. They promoted neurite outgrowth from PC12 cells and from dorsal root ganglion explants but only in the presence of nerve growth factor (NGF). We refer to these PGs as neurite outgrowth-promoting PGs (NEPPs). Through study of the structure-function relationship of NEPP1-10 and related compounds, we found that the cross-conjugated dienone moiety of NEPPs was essential for promoting neurite outgrowth, and NEPP10 was concluded to be the best candidate for drug development. We also investigated the intracellular mechanism of the promotion by NEPPs and obtained evidence that immunoglobulin heavy chain binding protein/glucose-regulated protein 78 (BiP/GRP78) plays a role in the promotion, based on the following observations: Antisense nucleotides for BiP/GRP78 gene blocked the promotion of neurite outgrowth; BiP/GRP78 protein level increased in response to NEPPs; and overexpression of BiP/GRP78 protein by adenoviral gene transfer promoted the neurite outgrowth by NGF.
Volume 75(3)
Pages 1092-102
Published 2000-9-1
DOI 10.1046/j.1471-4159.2000.0751092.x
PMID 10936191
MeSH Adenoviridae Animals Carrier Proteins / genetics Carrier Proteins / metabolism Cell Differentiation Cell Survival / drug effects Drug Design Genetic Vectors Heat-Shock Proteins* Molecular Chaperones / genetics Molecular Chaperones / metabolism Nerve Growth Factor / pharmacology* Neurites / drug effects Neurites / physiology* Neurons / cytology Neurons / drug effects Neurons / physiology* PC12 Cells Prostaglandins A / chemistry Prostaglandins A / pharmacology* Rats Recombinant Proteins / metabolism Structure-Activity Relationship Transfection
IF 4.87
Times Cited 51
DNA material Ax1 CA gfp (RDB01727)