| Project/Area Number |
11680559
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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 |
環境影響評価(含放射線生物学)
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
GOSHIMA Kiyota Kobe Gakuin University, Faculty of Humanities and Sciences, Associate Professor, 人文学部, 教授 (90111822)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Tadashi Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (80194398)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | lindane / hexachlorocyclohexane / gap junction / connexin43 / calcium / cardiotoxicity / cultured cardiac myocytes / ベンゼンヘキサクロリド / 心筋細胞 / カルシウムイオン / 環境汚染物質 / ミトコンドリア / 呼吸酵素 / ATP / 細胞内カルシウム / 非同期拍動 |
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| Research Abstract |
The effect of an environmental contaminant, lindane (γ-hexachlorocyclohexane), on gap junctional communication between cardiac myocytes is generally unknown, despite evidence that both acute andchronic lindane-induced cardiotoxicities were frequently accompanied to conduction disturbance. Toexplore the possibility that changes in gap junctional abnormalities induced by lindane might cause suchcardiotoxicities, we have investigated intercellular communication between cultured fetal mouse cardiacmyocytes treated with Lindane. Contractile activity of lindane-treated cells was characterized by regionalasynchrony as well as by increased [Ca^<2+>]. in cell-to-cell contact region. Junctional conductancebetween lindane-treated cell pairs was found to be lower than that of untreated cell pairs, i.e., therapidity and extent of intracellular transfer of the dye lucifer yellow was markedly reduced betweenlindane-treated cells. Immunocytochemical studies showed that the decrease of phosphorylatedconnnexin43, especcially their P2 form, was observed in lindane-treated cells. We also demonstratedthat the reduced phosphorylated connexin43 contents were due to the stimulated degradation ofubiquitin-dependent proteasomal proteolysis btlt not Ca^<2+>-calpain, lysosomal proteolysis, or the depressed synthetic protein pathway. These results suggested that lindane-induced inhibition of gap junctional communication in cultured cardiac myocytes may be a critical event associated with their cardiotoxicities.
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