The effect of intermedilysin on human bile duct cells
| Project/Area Number |
18592003
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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 |
Morphological basic dentistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HIROTA Katsuhiko The University of Tokushima, Institute of Health Bioscience Graduate School, associate professor (60199130)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKE Yoichiro The University of Tokushima, Institute of Health Bioscience Graduate School, professor (80136093)
NEMOTO Ken The University of Tokushima, Institute of Health Bioscience Graduate School, assistant professor (10218274)
村上 圭史 徳島大学, 大学院ヘルスバイオサイエンス研究部, 助手 (10335804)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | S.intermedius / intermedilysin / bile duct cells / non-apoptotic cell death / Ca^<2+> oscillation / BiP / calcineurin / NFAT / S.intermedius / インターメディリシン / CD59 / カルシウム振動 / 非アポトーシス / PTEN / Lamin B1 / 自己免疫性肝疾患 / アポトーシス |
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| Research Abstract |
Streptococcus intermedius is a commensal member of the human oral, gastrointestinal and urinary floras, but may also be associated with deep-seated purulent infections, particularly in the liver abscess.
It was recently reported that the function of bacterial pore-forming toxins is biphasic. Not only do they act cytolytically on nucleated target cells when present in higher concentrations, but they can also affect signal-transduction pathways in cells when the toxin is present in low, sublytic concentrations. Intermedilysin (ILY), a human-specific pore-forming cytolysin, has been suggested as a potentially important virulence factor of S.intermedius.
Whereas Ca^<2+> is a key regulator of cell survival, the breakdown of Ca^<2+> homeostasis due to its sustained elevation was able to trigger cell death. The goals here were to examine whether a low, sublytic concentration of ILY affects Ca^<2+> homeostasis in human bile duct cells by induction of [Ca^<2+>]I oscillation and [Ca^<2+>]I related
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other cell responses (the activation of calcineurin/NFAT pathway, PI3/AKT/MTOR pathway, and endoplasmic reticulum stress).
Fron the calcium imaging, five rain ILY treatment generated an increase in[Ca^<2+>]i level from the average base line of 50 nM up to the average peak of 400 nM marked by two repeated oscillations every minute. Increased [Ca^<2+>]i was initially detected in the nuclei of ILY-treated cells subsequently followed with markedly increase in ER area. Immunocytochemistry and Westernbloting analysis, ILY treatment caused activation of calcineurin/NFAT1 signalling pathway and increased expression of AKT(p-S473),BiP, and PTEN. Interestingly the expression of BiP and AKT(p-S473)decreased in an hour post ILY treatment. Calcineurin inhibitor cyclosporine A prevented ILY-induced calcineurin/NFAT1 activation, cell death, and calcium oscillations.
ILY in concentration of 10-40 ng/ml capable of inducing calcium oscillations, activation of calcineurin/NFAT1 signalling pathway ; inactivation of PI3K/AKT/MTOR pathway, and caused ER stress disorder resulted non-apoptotic cell death in HuCCT1 cells. Less
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Report
(3 results)
Research Products
(17 results)
