Gas6 rescues cortical neurons from amyloid β protein-induced apoptosis

• Published in: Neuropharmacology 2002-12, Vol.43 (8), p.1289-1296
• Main 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.
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Amyloid beta-Peptides - pharmacology; Amyloid beta-Peptides - physiology; Amyloid β protein; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Calcium - metabolism; Cell Death - drug effects; Cell Death - physiology; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Growth arrest-specific gene 6; Intercellular Signaling Peptides and Proteins; L-type voltage-dependent calcium channel; Medical sciences; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotection; Pharmacology. Drug treatments; Pregnancy; Proteins - pharmacology; Proteins - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(02)00333-7

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 Ca 2+ 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 Ca 2+ into neurons through L-VSCCs. Gas6 significantly inhibited the Aβ-induced Ca 2+ 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.