RGD Reference Report - Facilitatory roles of novel compounds designed from cyclopentenone prostaglandins on neurite outgrowth-promoting activities of nerve growth factor. - Rat Genome Database

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Facilitatory roles of novel compounds designed from cyclopentenone prostaglandins on neurite outgrowth-promoting activities of nerve growth factor.

Authors: 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 
Citation: Satoh T, etal., J Neurochem. 2000 Sep;75(3):1092-102.
RGD ID: 11354963
Pubmed: PMID:10936191   (View Abstract at PubMed)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to nerve growth factor stimulus  IEP 11354963 RGD 
positive regulation of neuron projection development  IMP 11354963 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspa5  (heat shock protein family A (Hsp70) member 5)


Additional Information