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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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | atherosclerosis / plaque rupture / LOX-1 / acute coronary syndrome / proteases / ADAM10 / IL-18 / shedding / トロンビン / メタロプロテアーゼ / 血栓 / LOX-1 / 動脈硬化 / マクロファージ / ガンマインターフェロン / ケモカイン / 平滑筋細胞 / CXCR6 |
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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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Report
(3 results)
Research Products
(22 results)
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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
Related Report
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
Related Report
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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
Related Report
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[Journal Article] Serum soluble ectin-like oxidized low-density lipoprotein recepfor-1 levels are elevated in acute coronary syndrome. A novel marker for early diagnosis.2005
Author(s)
Kazutaka Hayashida, Noriaki Kume, Takatoshi Murase T, Manabu Minami, Daisuke Nakagawa, Tsukasa Inada, Masaru Tanaka Akira Ueda, Goro Kominami, Horofumi Kambara, Takeshi Kimura, Toru Kita
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Journal Title
Circulation 112
Pages: 812-818
Related Report
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