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LTRPC2 Ca2+-permeble channel activated by changes in redox status confers susceptibility to cell death
https://ir.soken.ac.jp/records/1122
https://ir.soken.ac.jp/records/1122e0470c29-bb7c-4a1c-b43e-10759cc893c1
| 名前 / ファイル | ライセンス | アクション |
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要旨・審査要旨 / Abstract, Screening Result (228.1 kB)
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本文 (2.0 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2010-02-22 | |||||
| タイトル | ||||||
| タイトル | LTRPC2 Ca2+-permeble channel activated by changes in redox status confers susceptibility to cell death | |||||
| タイトル | ||||||
| タイトル | LTRPC2 Ca2+-permeble channel activated by changes in redox status confers susceptibility to cell death | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| 著者名 |
原, 雄二
× 原, 雄二 |
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| フリガナ |
ハラ, ユウジ
× ハラ, ユウジ |
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| 著者 |
HARA, Yuji
× HARA, Yuji |
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| 学位授与機関 | ||||||
| 学位授与機関名 | 総合研究大学院大学 | |||||
| 学位名 | ||||||
| 学位名 | 博士（理学） | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 総研大甲第618号 | |||||
| 研究科 | ||||||
| 値 | 生命科学研究科 | |||||
| 専攻 | ||||||
| 値 | 20 生理科学専攻 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2002-03-22 | |||||
| 学位授与年度 | ||||||
| 値 | 2001 | |||||
| 要旨 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Redox status changes exert critical impacts on necrotic/apoptotic and normal cellular processes. Key contributors to altered cellular redox status are reactive oxygen species (ROS) and reactive nitrogen species (RNS) which are generated by exogenous genotoxic agents such as inflammatory cytokines or chemical carcinogens.<br /> Regulation of intracellular Ca2+ concentration ([Ca2+]i) also plays critical roles in both normal cellular functions and pathological cell degenerations. In acute insults such as hypoxia-ischemia, it has been proposed that the resultant cell fate (necrosis, apoptosis, survival) is dependent on an intracellular 'Ca2+ setpoint'. However, the molecular mechanisms of excessive Ca2+ influx in response to redox dyshomeostasis is still controversial.<br /> He has identified a Ca2+-permeable cation channel LTRPC2 activated by changes in cellular redox status. LTRPC2, originally discovered as a homologue of Drosophila transient receptor potential, belongs to 'Long' IRP family. LTRPC2 showed abundant RNA expression in the lung, spleen, eye, and brain. LTRPC2 elicited Ca2+-entry in response to extracellular H2O2, at concentrations of micromolar range, in contrast to other types of Ca2+ channels which require much higher H2O2 concentrations, and under various conditions that generate ROS. Patch-clamp recordings and biochemical experiments demonstrated that the sensitivity of LTRPC2 to redox state modifiers was attributable to an agonistic binding of nicotinamide adenine dinucleotide (β-NAD+) to the MutT motif. Arachidonic acid and Ca2+ were important positive regulators for LTRPC2. Heterologous LTRPC2 expression conferred susceptibility to death on HEK cells. Moreover, antisense oligonucleotide experiments revealed physiological involvement of 'native' LTRPC2 in H2O2-- and TNF α-induced Ca2+ influx and cell death in rat insulinoma RIN-5F and human monocyte U937. Thus, LTRPC2 represents an important intrinsic mechanism that mediates Ca2+ and Na+ overload in response to disturbance of redox state in cell death. | |||||
| 所蔵 | ||||||
| 値 | 有 | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
