| Project/Area Number |
15591238
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SOHMA Hitoshi SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (70226702)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Toshikazu SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (50128518)
HASHIMOTO Eri SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (30301401)
KUROKI Yoshio SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (70161784)
小澤 寛樹 長崎大学, 医学部, 教授 (50260766)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | ALCOHOL / DEPENDENT DRUG / CELL DAMAGE / CALCIUM STRESS / DEMENTIA / ANNEXIN / 神経栄養因子 / 分化 / 神経家用因子 / BDNF / CREB / アポトーシス / Ca^<2+>-イオノフォア / 転写調節因子 / アルコール障害 / アルツハイマー病 / ストレス障害 |
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| Research Abstract |
Chronic ingestion of ethanol upregulates the Ca^<2+> channel activity, which in turn increases the intracellular Ca^<2+>-concentration, resulting in neuronal cell damage. Intracellular elevation of Ca^<2+> via the activation of Ca^<2+> channel is also revealed in dementia such as Alzheimer's disease (AD), etc. In the present study, it was shown that ethanol exposure to cultured neuronal cells augments annexin A4 expression and accompanied by the activation of NF-κB. Annexin A4 directly bound to NF-κB and the Ca^<2+> binding sites on annexin A4 were involved in this event. We further investigated the quantitative alteration of the secreted proteins by Ca^<2+>-stress with neuronal culture cells. The amounts of secreted proteins were investigated after exposure to Ca^<2+>-ionophre (A23187) under the condition where cell viability was comparable with untreated control. Several proteins were shown to be increased by A23187. After two dimensional-gel electrophoresis, the proteins were identified by LC-MS spectrometry. The data base searching indicated that these three spots are annexin A2, fetuin, annexin A5 and SLUG. These proteins might be biological markers of dementia. We next focused on annexin A5 and analyzed it in blood plasma of dementia patients using sandwich ELISA. It was shown that plasma level of annexin A5 was significantly higher in dementia patients (AD, vascular and alcoholic dementia) than in healthy controls. However, it is hard to detect early stage of AD by this method. The physiological feature of these proteins in the etiology of AD is uncovered in the next step.
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