2004 Fiscal Year Final Research Report Summary
PROTECTIVE EFFECT OF SPHINGOSINE 1-PHOSPHATE ON LIVER SINUSOIDAL ENDOTHELIAL CELLS AGAINST ETHANOL-INDUCED APOPTOSIS
| Project/Area Number |
15590689
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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 |
Gastroenterology
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| Research Institution | JUNTENDO UNWARILY |
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Principal Investigator |
KITAMURA Tsuneo JUNTENDO UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (20231285)
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| Co-Investigator(Kenkyū-buntansha) |
ENOMOTO Nobuyuki JUNTENDO UNIVERSITY, INSTRUCTOR, 医学部, 助手 (20348973)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Alcoholic Liver Injury / Liver Sinusoidal Endothelial Cells / Syhingosine 1-Phosphate / Apoptosis / Calcium |
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| Research Abstract |
The mechanism of alcoholic liver disease has been largely investigated in parenchymal hepatocyte. However, little is known about the mechanisms underlying the protection of sinusoidal endothelial cells (SECs) against ethanol-induced injury. Recently, sphingosine 1-phosphate (S1P), a serum-borne bioactive lipid released from activated platelets, has been reported to regulate diverse biological processes, such as cell proliferation, migration, wound healing and inhibition of apoptosis. To test whether S1P may affect biological function of SECs in ethanol-induced liver injury, we examined the effect of extracellular S1P on SECs in primary culture.
Our results show that S1P protects SECs against ethanol-induced injury in primary culture of rat liver, and that the protective effect of S1P may be mediated by activation of Ca^<2+>-sensitive eNOS and subsequent NO formation. This is consistent with previous report that NO generated by eNOS is important for protection of apoptosis in several cell types, and further supported by our present finding that inhibition of calmodulin, a Ca^<2+> binding protein, attenuates S1P-induced eNOS activity in SECs. S1P also ameliorated the decreased DNA synthesis of cells caused by ethanol. We thus propose that S1P, which is possibly released from activated platelets in response to ethanol consumption, could contribute to sinusoidal protection and remodeling in alcoholic liver injury.
Although further research is required to elucidate the molecular interaction between Ca^<2+>, CaM and eNOS activity, our results suggest a possible mechanism for the regulation of ethanol-induced apoptosis in SECs by S1P. Physiological importance of S1P is uncertain. However, our findings may lead to a better understanding of S1P as a target for novel therapeutic strategies in alcoholic liver injury.
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Research Products
(12 results)
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[Journal Article] Senescence marker protein-30 regulates Akt activity and contributes to cell survival in Hep G2 cells.2004
Author(s)
Matsuyama S, Kitamura T, Enomoto N, Fujita T, Ishigami A, Handa S, Maruyama N, Zheng D, Ikej ima K, Takei Y, Sato N.
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Journal Title
Biochem Biophys Res Conunun 321
Pages: 386-390
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Senescence marker protein-30 regulates Akt activity and contributes to cell survival in Hep G2 cells.2004
Author(s)
Matsuyama S, Kitamura T, Enomoto N, Fujita T, Ishigami A, Handa S, Maruyama N, Zheng D, Ikejima K, Takei Y, Sato N.
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Journal Title
Biochem Biophys Res Commun 321
Pages: 386-390
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prevention of Ethanol-Induced Liver Injury in Rats by an Agonist of PPAR{gamma}, Pioglitazone.2003
Author(s)
Enomoto N, Takei Y, Hirose M, Konno A, Shibuya T, Matsuyama S, Suzuki S, Ikejima K, Kitamura T, Sato N
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Journal Title
J Pharmacol Exp Ther 306
Pages: 846-854
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Prevention of Ethanol-Induced Liver Injury in Rats by an Agonist of PPAR {gamma}, Pioglitazone.2003
Author(s)
Enomoto N, Takei Y, Hirose M, Konno A, Shibuya T, Matsuyama S, Suzuki S, Ikejima K, Kitamura T, Sato N.
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Journal Title
Pharmacol Exp Ther 306
Pages: 846-854
Description
「研究成果報告書概要(欧文)」より
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[Book] Role of sphingosine 1-phosphate in protection of liver sinusoidal endothelial cells against ethanol-induced apoptosis. Microcirculation Annual 20052005
Author(s)
Zheng D-M, Kitamura T, Ikejima K, Enomoto N, Yamashina S, Suzuki S, Takei Y, Sato N.
Total Pages
55-56
Publisher
Asano M, oda M (eds), 21, NIHON-IGAKUKAN :
Description
「研究成果報告書概要(和文)」より
