2005 Fiscal Year Final Research Report Summary
Oxidized LDL receptors, LOX-1 and SE-PSOX and their soluble molecules
| Project/Area Number |
16590880
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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 |
Metabolomics
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| Research Institution | Kyoto University |
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Principal Investigator |
KUME Noriaki Kyoto University, Department of Cardiovascular Medicine, Associate Professor (20252455)
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| Project Period (FY) |
2004 – 2005
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| Keywords | atherosclerosis / plaque rupture / LOX-1 / acute coronary syndrome / proteases / ADAM10 / IL-18 / shedding |
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| Research Abstract |
Lectin-like oxidized LDL receptor-1 (LOX-1) appears to play crucial roles in atherosclerotic plaque rupture. We previously reported that circulating soluble LOX-1 (sLOX-1) levels are elevated in acute coronary syndrome (ACS) and that sLOX-1 can be a specific and sensitive biomarker for ACS. A proinflammatory cytokine interleukin 18 (IL-18) and its receptor are prominently expressed in atherosclerotic plaques. In addition, circulating IL-18 levels were reported to be high in ACS. In this study, we have examined if IL-18 can stimulate shedding of LOX-1 and subsequent release of sLOX-1. After transfection with LOX-1 cDNA, HEK-293T cells were incubated with or without IL-18. Cell-conditioned media and total cell lysates were subjected to immunoblot analyses with an anti-LOX-1 monoclonal antibody. In addition, ADAM10 cDNA, ADAM10 siRNA or control vector were also co-transfected into HEK-293T cells, and the cell-conditioned media and total cell lysates were subjected to LOX-1 immunoblotting after treatment with or without IL-18. The cell-conditioned medium/total cell lysate ratios in the amounts of LOX-1 or sLOX-1 were determined as sLOX-1 cleavage ratios. IL-18 (10-100 ng/ml) stimulation increased the sLOX-1 cleavage by 3- to 4-fold in a concentration- and time-dependent manner. ADAM10 overexpression alone similarly enhanced the sLOX-1 cleavage. ADAM10 inhibition by ADAM10 siRNA transfection significantly suppressed IL-18-induced sLOX-1 cleavage. IL-18 similarly enhanced sLOX-1 cleavage in TNF-〓-activated cultured endothelial cells, as well as LOX-1 transgenic mice in vivo. IL-18 appears one of the stimuli that enhance sLOX-1 release in ACS and ADAM10 may be involved in this process.
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[Journal Article] Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are elevated in acute coronary syndrome. A novel marker for early diagnosis.2005
Author(s)
Hayashida K, Kume N, Murase T, Minami M, Nakagawa D, Inada T, Tanaka M Ueda A, Kominami G, Kambara H, Kimura T, Kita T
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Journal Title
Circulation 112
Pages: 812-818
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] CXCL16 is a novel angiogenic factor for human umbilical vein endothelial cells2005
Author(s)
Xin, Zhuge, Toshinori, Murayama, Hidenori, Arai, Ryoko, Yamauchi, Makoto, Tanaka, Takeshi, Shimaoka, Shin, Yonehara, Noriaki, Kume, Masayuki, Yokode, Toru, Kita
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Journal Title
Biochem. Biophys. Res. Commun 331
Pages: 1295-1300
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are elevated in acute coronary syndrome. A novel marker for early diagnosis2005
Author(s)
Hayashida, K., Kume, N., Murase, T., Minami, M., Nakagawa, D., Inada, T., Tanaka, M., Ueda, A., Kominami, G., Kambara, H., Kimura, T., Kita, T
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Journal Title
Circulation 112
Pages: 812-818
Description
「研究成果報告書概要(欧文)」より
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