1997 Fiscal Year Final Research Report Summary
Studies on the regulation of cholesteryl ester synthesis and mechanism of lipid accumulation in macrophage cells
| Project/Area Number |
07457228
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
YAMAMURA Taku National Cardiovascular Center Research Institute, Department of Etiology and Pahtophysiology, Head of Laboratory, 病因部, 室長 (20132938)
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| Co-Investigator(Kenkyū-buntansha) |
SIGANO Ryo National Cardiovascular Center Research Institute, Department of Etiology and Pa, 病因部, レジデント研究員
KAWAGUCHI Akito National Cardiovascular Center Research Institute, Department of Etiology and Pa, 病因部, 室員 (70214608)
MIYAKE Yasuko National Cardiovascular Center Research Institute, Department of Etiology and Pa, 病因部, 室長 (00132936)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Apolipoprotein / Atherosclerosis / Cholesterol / Low-density lipoprotein / Macrophage / Scavenger receptor / Transforming growth factor-beta1 |
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| Research Abstract |
Macrophage cells derived from the human monocytic leukemia cell line, THP-1, accumulate esterified cholesterol when cultivated in the presence of acetylated low-density lipoprotein(Ac-LDL) through scavenger receptors (ScR). In the present study, we isolated a subtype of THP-1 cells that failed to accumulate esterified cholesterol when cultivated in the presence of Ac-LDL.The cells had negligible amounts of cell-association and degradation of Ac-LCL compared to the parent THP-1 cell. The subtype THP-1 cells did not express ScR mRNA as well as that of lipoprotein lipase. In contrast, the expression of apolipoprotein E mRNA was greater than that found in parent THP-1 cells. The culture medium of subtype THP-1 cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) inhibited the uptake of Ac-LDL and the expression of ScR in parent THP-1 cells. After 48 h incubation in the culture medium containing TPA,the culture medium of differentiated subtype THP-1 cells contained 6.9 ng/ml of tr
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ansforming growth factor (TGF)-beta1, while that of parent THP-1 cells secreted below detection level, which was less than 3 ng/ml. This inhibitory effect of the conditioned medium on the expression of ScR in parent THP-1 cells was abolished by pre-treatment of the culture medium with anti-TGF-beta1 antibodies. Parent THP-1 cells expressed as much amount of TGF-beta1 mRNA as sTHP-1 cells after stimulation of differentiation. Although the precursor forms of TGF-beta1 which were synthesized in both parent and subtype THP-1 cells were of similar size and were expressed at similar levels, latent TGF-beta1-binding protein (LTBP), which is necessary for the secretion of TGF-beta1, could only be co-immunoprecititated with anti- TGF-beta1 antibody from subtype THP-1 cells. This suggests that subtype THP-1 cells secrete TGF-beta1 into the medium by forming a functional complex with LTBp. We conclude that subtype THP-1 cells could not take up Ac-LDL because ScR was inhibited (leading a loss of function) caused by the secreted TGF-beta1. Less
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[Publications] Yamamura, T., Nomura, S., Yang, X., Yamamoto, A., Haze, K., Hiramori, K., Hara, H., Yamaguchi, T., and Pokrovsky, S.N.: "Lipoprotein(a) in ishemic herat disease and cerebrovascular disease." J.Atheroscler.Thromb. 2 (Suppl.1). S13-S16 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Maruyama, T., Miyake, Y., Tajima, S., Harada-Shiba, M., Yamamura, T., Tsushima, M., Kishino, B., Horiguchi, Y., Junahashi, T., Matsuzawa, Y.and Yamamoto, A.: "Common Mutations in the low-density-lipoprotein-receptor gene causing familial hypercholesterolemia in the Japanese population." Arterioscler.Thromb.Vasc.Biol.15. 1713-1718 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Harada-Shiba, M., Yamamura, T., Toyota, Y., Tsushima, M., Kojima, S.and Yamamoto, A.: "Kinetic analysis of cholesterol and Lp(a) using the rebound curve after LDL-apheresis." Jpn.J.Aphersis. 15. 96-97 (1995)
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[Publications] Yu, K.C.-W., Smith, D., Yamamoto, A., Kawaguchi, A., Harada-Shiba, M., Yamamura, T.and Momo, J.C.L.: "Phagocytic degradation of chylomicron remnants by fibroblasts from subjects with homozygous familial hypercholesterolemia." Clin.Sci.92. 197-203 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Maruyama, T., Miyake, Y., Yamamura, T., Tajima, S., Funahashi, T., Matsuzawa, Y.and Yamamoto, A.: "Anovel mutation in a splice acceptor site of intron 1 of the human low density lipoprotein receptor gene which causes severe hypercholesterolemia : an unexpected absence of exon skipping." Hum.Mutat., Mutation in Brief. #139 (On-line). (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Varret, M., Robes, J.-P., Thiart, R., Kotze, M.J., Baron, H., Cenarro, A., Descamps, O., Ebhardt, M., Hondeliji, J.-C., Kostner, G.M., Miyake, Y., Pocovi, M., Schmidt, H., Schmidt, H., Schuster, H., Stuhrmann, M., Yamamura, T., Junien, C., Beroud, C.and Boileau, C.: "LDLR databese (second edition) : new additions to the databese and the software, and results of the first molecular analysis." Nucleic Acid Res.26. 248-252 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Nishimura, N., Harada-Shiba, M., Tajima, S., Sugano, R., Yamamura, T., Qiang, Q.Z.and Yamamoto, A.: "Acquisition of secretion of transforming growth factor-beta1 leads to autonomous suppression of scavenger receptor activity in a monocyte-macrophage cell line THP-1." J.Biol.Chem.273. 1562-1567 (1998)
Description
「研究成果報告書概要(欧文)」より
