Facilitatory Roles of Novel Compounds Designed from Cyclopentenone Prostaglandins on Neurite Outgrowth-Promoting Activities of Nerve Growth Factor
| Autor: | Kyoji Furuta, Daisaku Nakatsuka, Masaaki Suzuki, Kazuyoshi Ikuta, Yasuyoshi Watanabe, Tetsuro Koike, Motoki Tanikawa, Takumi Satoh, Keiichiro Tomokiyo, Hiroshi Hatanaka, Shuuitsu Tanaka, Makoto Nakanishi, Maki Miura |
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| Rok vydání: | 2002 |
| Předmět: |
Cyclopentenone
Neurite Cell Survival Genetic Vectors Biology Transfection PC12 Cells Biochemistry Adenoviridae Structure-Activity Relationship Cellular and Molecular Neuroscience chemistry.chemical_compound Dorsal root ganglion Nerve Growth Factor Neurites medicine Animals Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins Cyclopentenone prostaglandins Neurons Prostaglandins A Cell Differentiation Cell cycle Recombinant Proteins Rats Cell biology medicine.anatomical_structure Nerve growth factor chemistry Cell culture Drug Design Carrier Proteins Intracellular Molecular Chaperones |
| Zdroj: | Journal of Neurochemistry. 75:1092-1102 |
| ISSN: | 0022-3042 |
| Popis: | Cyclopentenone prostaglandins (PGs) are known to arrest the cell cycle at the G1 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. |
| Databáze: | OpenAIRE |
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