Gas6 rescues cortical neurons from amyloid beta protein-induced apoptosis |
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Authors: | Yagami T Ueda K Asakura K Sakaeda T Nakazato H Kuroda T Hata S Sakaguchi G Itoh N Nakano T Kambayashi Y Tsuzuki H |
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Affiliation: | Discovery Research Laboratories, Shionogi and Co., Ltd., 12-4 Sagisu 5-Chome, Fukushima-ku, Osaka 553-0002, Japan |
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Abstract: | Gas6, a product of the growth-arrest-specific gene 6, protects neurons from serum deprivation-induced apoptosis. Neuronal apoptosis is also caused by amyloid β protein (Aβ), whose accumulation in the brain is a characteristic feature of Alzheimer’s disease. Aβ induces Ca2+ influx via L-type voltage-dependent calcium channels (L-VSCCs), leading to its neurotoxicity. In the present study, we investigated effects of Gas6 on Aβ-induced cell death in primary cultures of rat cortical neurons. Aβ caused neuronal cell death in a concentration- and time-dependent manner. Gas6 significantly prevented neurons from Aβ-induced cell death. Gas6 ameliorated Aβ-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. Prior to cell death, Aβ increased influx of Ca2+ into neurons through L-VSCCs. Gas6 significantly inhibited the Aβ-induced Ca2+ influx. The inhibitor of L-VSCCs also suppressed Aβ-induced neuronal cell death. The present cortical cultures contained few non-neuronal cells, indicating that Gas6 affected the survival of neurons directly, but not indirectly via non-neuronal cells. In conclusion, we demonstrate that Gas6 rescues cortical neurons from Aβ-induced apoptosis. Furthermore, the present study indicates that inhibition of L-VSCC contributes to the neuroprotective effect of Gas6. |
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Keywords: | Alzheimer’s disease Amyloid β protein Growth arrest-specific gene 6 L-type voltage-dependent calcium channel Apoptosis Neuroprotection |
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