Altered structure of LDL receptor and cholesterol metabolic defects.

LDL 受体结构改变和胆固醇代谢缺陷。

• 批准号: 62480134
• 负责人: KUWANO Michihiko
• 金额: $ 4.22万
• 依托单位: Medical College of Oita
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480134/
• 关键词: Low density lipoprotein; LDL receptor; LDL receptor mutation; Cholesterol metabolic disorders; Carbohydrate chain mutation; Macrophage; 泡沫化細胞; 低比重リポ蛋白(LDL); 糖鎖構造異変; 体細胞遺伝変異; 低比重リポ蛋白レセプター不全; ゴルジ装置

Hypercholesterolemia and atherosclerosis are plausibly main origins for hypertension. We have established two systems of model cell lines in culture for altered cholesterol metabolic disease and also atheromatous foam cells.First system is to establish and characterize somatic cell mutants with defects in the regulation of sterol metabolism. We have selected animal cell mutants with very high sterol synthesis, and they carry low density lipoprotein (LDL) receptors with altered sugar chains. These mutants are supposed to affect Golgi apparatus function. discovery of this new gene, int, may imply a further etiology for hypercholesterolemia.Second system is to study mechanism for appearance of atheromatous foam cells by using established mouse macrophage J774 cell line in culture. J774 cells are loaded with cholesterol esters when native LDL is challenged. Analysis of biosynthesis, processing and degradation of LDL receptors of J774 cells shows very rapid rate of degradation of LDL receptors in comparison with other non-macrophage cell lines. This model system with macrophage cell line might imply new idea for involvement of native LDL in earlier atherosclerosis change besides scavenger pathway model with denatured LDL.

高胆固醇血症和动脉粥样硬化似乎是高血压的主要原因。我们已经建立了两个系统的模型细胞系，用于改变胆固醇代谢疾病以及动脉粥样硬化泡沫细胞。第一个系统是建立和表征在甾醇代谢调节方面存在缺陷的体细胞突变体。我们选择了甾醇合成非常高的动物细胞突变体，它们携带糖链发生改变的低密度脂蛋白（LDL）受体。这些突变体应该会影响高尔基体功能。这个新基因int的发现可能意味着高胆固醇血症的进一步病因学。第二个系统是通过使用已建立的小鼠巨噬细胞J774细胞系来研究动脉粥样化泡沫细胞出现的机制。当天然 LDL 受到挑战时，J774 细胞会装载胆固醇酯。对 J774 细胞 LDL 受体生物合成、加工和降解的分析表明，与其他非巨噬细胞系相比，LDL 受体的降解速度非常快。除了具有变性 LDL 的清道夫途径模型之外，这种具有巨噬细胞系的模型系统可能意味着天然 LDL 参与早期动脉粥样硬化变化的新思路。

项目成果

Yuichiro Kuratomi: Journal of Cellular Physiology. 130. 51-57 (1987)

仓富雄一郎：细胞生理学杂志。

桑野信彦: 組織培養. 13. 216-221 (1987)

桑野信彦：组织培养。13。216-221（1987）

Tadashi Seguchi: Journal of Cellular Physiology. in press. (1989)

Tadashi Seguchi：细胞生理学杂志。

Akihiko Yoshimura: Biochimica et Biophysica Acta. 904. 159-164 (1987)

吉村明彦：生物化学与生物物理学学报。

Satoshi Shite: Journal of Biological Chemistry. 263. (1988)

Satoshi Shite：生物化学杂志。