Prostaglandin E2 rescues cortical neurons from amyloid β protein-induced apoptosis
| Autor: | Naohiro Itoh, Yutaka Hashimoto, Hitoshi Nakazato, Yoshikazu Kambayashi, Tsuzuki Hiroshige, Takayuki Kuroda, Kenji Asakura, Gaku Sakaguchi, Toshiyuki Sakaeda, Satoshi Hata, Tatsurou Yagami, Keiichi Ueda |
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| Rok vydání: | 2003 |
| Předmět: |
endocrine system
medicine.medical_specialty Programmed cell death Apoptosis Biology Neuroprotection Dinoprostone Rats Sprague-Dawley Internal medicine medicine Animals Neurotoxin Prostaglandin E2 Molecular Biology Cells Cultured Cerebral Cortex Neurons Amyloid beta-Peptides Dose-Response Relationship Drug General Neuroscience Calcium channel Neurodegeneration Neurotoxicity medicine.disease Rats Neuroprotective Agents Endocrinology lipids (amino acids peptides and proteins) Neurology (clinical) Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 959:328-335 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/s0006-8993(02)03773-3 |
| Popis: | Cerebrospinal fluid prostaglandin E(2) (PGE(2)) levels are elevated in patients with Alzheimer's disease (AD), suggesting an involvement of PGE(2) in the neurodegeneration. AD is characterized by deposits of amyloid beta protein (Abeta) in various regions of the brain, e.g. the cerebral cortex. In the present study, we investigated the effects of PGE(2) on neuronal survival in primary cultures of rat cortical neurons. PGE(2) had no effect on neuronal cell viability or its morphology. Therefore, we examined the synergistic effects of PGE(2) with Abeta, a neurotoxin. Abeta caused neuronal cell death via apoptosis. PGE(2) significantly suppressed Abeta neurotoxicity, but did not promote the neurotoxicity. Furthermore, PGE(2) ameliorated Abeta-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. Abeta increased the influx of Ca(2+) into neurons before cell death. Nimodipine, an inhibitor of the L-type voltage-sensitive calcium channel (L-VSCC), significantly reduced Abeta-potentiated Ca(2+) uptake. On the other hand, there was no effect on the Abeta-induced Ca(2+) influx by an N-VSCC blocker or P/Q-VSCC blockers. Moreover, the inhibitor of L-VSCC suppressed Abeta-induced neuronal cell death, whereas neither an N-VSCC blocker nor P/Q-VSCC blockers affected the neurotoxicity of Abeta. PGE(2) also suppressed the Abeta-induced Ca(2+) influx in a concentration-dependent manner. This study demonstrated that PGE(2) rescues cortical neurons from Abeta-induced apoptosis by reducing Ca(2+) influx in the primary culture. Furthermore, the present study suggested that the inhibition of L-VSCC contributes to the neuroprotective effect of PGE(2). |
| Databáze: | OpenAIRE |
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