2004 Fiscal Year Final Research Report Summary
Effects of nicotinic acetylcholine receptor overexpression in neuronal cells.
| Project/Area Number |
14570614
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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 |
Neurology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
UTSUGISAWA Kimiaki Iwate Medical University, Neurology, Lecturer, 医学部, 講師 (00244913)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANE Yuriko Iwate Medical University, Neurology, Instructor, 医学部, 助手 (10306003)
YAMAGATA Munehisa Iwate Medical University, Neurology, Instructor, 医学部, 助手 (00295974)
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| Project Period (FY) |
2002 – 2004
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| Keywords | α7nAChR / Angiotensin II / Cell cycle / Extracellular-signal-regulated kinase / Hypoxia / Neurite outgrowth / PC12 / Protein kinase Cδ |
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| Research Abstract |
PC12 cells transfected with the α7nAChR cDNA, independent of agonistic stimulation, exhibited to start the sustained expression of phospho-extracellular-signal-regulated kinases (ERKs) as immediately as expression of α 7 subunit protein after transfection. PC12 cells over-expressing α7nAChR showed high migration ability, marked neurite outgrowth, adherence to the culture dish and an increase in expression of surface N-cadherin, whereas their proliferation activity was low. Examination of cell cycle distribution showed an increase in the proportion of G2-phase cells in PC12 cells over-expressing α 7nAChR. These findings suggest that, over-expression of α7nAChR induces sustained activation of ERK, which probably promotes the functions of neuron-specific Cdks and differentiation-like transformation. The cytoskeletal machinery necessary for sufficient expression of α7nAChR may have some links to ERK and Cdk signals promoting neurite outgrowth, and their declines in the elderly may deterior
… More
ate neuronal plasticity.
To investigate the role of protein kinase Cδ (PKCδ) in angiotensin II -induced facilitation mechanisms of hypoxic neuronal damage and whether candesartan, an AT1 receptor antagonist, can suppress these mechanisms, we performed in vitro experiments using PC12 cells under hypoxic/reoxygenation conditions. Angiotensin II increased the basal expression level of PKCδ phosphorylated at Ser643 before hypoxia, promoted the cleavage of PKC δ to its catalytic fragment, and fostered the progression of DNA fragmentation after hypoxia. Candesartan inhibited both phosphorylation and cleavage of PKCδ and suppressed the angiotensin II -induced facilitation of DNA fragmentation. In PC12 cells expressing the ATP-binding mutant of PKCδ acting as a dominant-negative protein, DNA fragmentation was markedly suppressed regardless of the presence of angiotensin II. These findings suggest that angiotensin II -induced facilitation of DNA fragmentation under hypoxic conditions is mediated by PKCδ, and the mechanisms can be suppressed by the candesartan mediated blockade of the AT1 receptor. Less
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Research Products
(15 results)
