Ongoing insulin therapy maintains LDL receptors at highly expressed state in Type-1 diabetic people;yet Type-1 diabetics are liable of having higher plasma LDL level. This disparity has raised doubt on the probability...Ongoing insulin therapy maintains LDL receptors at highly expressed state in Type-1 diabetic people;yet Type-1 diabetics are liable of having higher plasma LDL level. This disparity has raised doubt on the probability of existence of functionally active LDL receptor in such people. Confocal microscopy and immunoprecipitation have made it evident that a portion of insulin and LDL receptors remain together in a co-localized mode, which only gets freed in presence of insulin. The findings of this study have shown that insulin therapy protects Type-1 diabetic people from the pathogenesis of atherosclerosis by decimating the inactivity of the co-localized LDL receptors in addition to its regular effect of having increased glucose tolerance. The existence of co-localized state of these two receptors and their dependence on insulin for independent activity has, at least, presented a reason for developing hypercholesterolemia and advanced coronary atherosclerotic lesion in chronic Type-1 diabetic subjects.展开更多
Low density lipoprotein (LDL) receptor is a cell surface glycoprotein that regulates plasma cholesterol by mediating endocytosis of LDL and supplies cells with cholesterol. LDL receptor was first identified in 1973 by...Low density lipoprotein (LDL) receptor is a cell surface glycoprotein that regulates plasma cholesterol by mediating endocytosis of LDL and supplies cells with cholesterol. LDL receptor was first identified in 1973 by Goldstein and Brown, who won the Nobel Prize in 1985. Mutations in the LDL receptor gene cause familial hyper-cholesterolemia (FH), a common disease that affects about 1 in 500 people in most populations. Individuals heterozygous for LDL receptor mutation in one allele express half the normal number of functional receptors on their cell surface. This produces a two-fold elevation in plasma LDL-cholesterol concentration. The excess plasma LDL-cholesterol deposits in tendons and arterial walls, forming tendon xanthomas and atherosclerotic plaques. The rare FH homozygotes (about 1 per million people) have mutations in both LDL receptor genes, express few or no functional LDL receptors on their cell surfaces. Their plasma LDL-cholesterol level rises dramatically and displays a pathognomonic sk展开更多
We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on ...We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on LDL receptor gene expression in a human hepatoma cell line (HepG2) treated with Dai-saiko-to extract and the extracts of eight herbs presented in Dai-saiko-to. Dai-saiko-to extract significantly increased LDL receptor gene and SREBP2 gene expression compared with the control. The extracts of four herbs, Bupleurum root, Pinellia tuber, Scutellaria root and Peony root significantly increased the LDL receptor gene expression. Whereas, Jujube, Immature orange, Ginger and Rhubarb extracts did not change the gene expression. These results suggest that Dai-saiko-to increased the expression of the cholesterol transport gene (LDL receptor) regulated by SREBP2 gene in the human hepatoma cell line. The pharmacological activity of Dai-saiko-to against hypercholesterolemia and atheromatous lesions related for these four herbal components.展开更多
文摘Ongoing insulin therapy maintains LDL receptors at highly expressed state in Type-1 diabetic people;yet Type-1 diabetics are liable of having higher plasma LDL level. This disparity has raised doubt on the probability of existence of functionally active LDL receptor in such people. Confocal microscopy and immunoprecipitation have made it evident that a portion of insulin and LDL receptors remain together in a co-localized mode, which only gets freed in presence of insulin. The findings of this study have shown that insulin therapy protects Type-1 diabetic people from the pathogenesis of atherosclerosis by decimating the inactivity of the co-localized LDL receptors in addition to its regular effect of having increased glucose tolerance. The existence of co-localized state of these two receptors and their dependence on insulin for independent activity has, at least, presented a reason for developing hypercholesterolemia and advanced coronary atherosclerotic lesion in chronic Type-1 diabetic subjects.
文摘Low density lipoprotein (LDL) receptor is a cell surface glycoprotein that regulates plasma cholesterol by mediating endocytosis of LDL and supplies cells with cholesterol. LDL receptor was first identified in 1973 by Goldstein and Brown, who won the Nobel Prize in 1985. Mutations in the LDL receptor gene cause familial hyper-cholesterolemia (FH), a common disease that affects about 1 in 500 people in most populations. Individuals heterozygous for LDL receptor mutation in one allele express half the normal number of functional receptors on their cell surface. This produces a two-fold elevation in plasma LDL-cholesterol concentration. The excess plasma LDL-cholesterol deposits in tendons and arterial walls, forming tendon xanthomas and atherosclerotic plaques. The rare FH homozygotes (about 1 per million people) have mutations in both LDL receptor genes, express few or no functional LDL receptors on their cell surfaces. Their plasma LDL-cholesterol level rises dramatically and displays a pathognomonic sk
基金supported by grants from the Youth Innovative Talents Program and Characteristic Innovative Talents Program of Regular Institutions of Higher Education of Guangdong Province(2018KQNCX212,2020KTSCX101)the Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong Province(20222122)+3 种基金the Excellent Youth Science Research Program of the Education Department of Hunan Province(14B183)Bureau of Education of Guangzhou Municipality(202032801)the Plan on Enhancing Scientific Research in Guangzhou Medical Universitythe Open Research Funds(2021)and the Funds of Selected Project(2022)from GMU-GIBH Joint School of Life Sciences,Guangzhou Medical University。
文摘目的oxLDL可上调Plin2的表达,进而促进泡沫细胞的形成,LOX1是oxLDL的受体。本文探讨Plin2与LOX1在动脉粥样硬化发生发展过程中的关系。方法从GEO数据库中下载GSE43292,分析Plin2、LOX1的表达及Plin2、LOX1与NF-κB信号通路的相关性。采用oxLDL处理的RAW264.7细胞作为动脉粥样硬化的细胞模型进行研究,蛋白质免疫印迹法检测细胞中Plin2、LOX1和p-p65的表达,荧光中性脂质染料BODIPY 493/503染色法检测细胞内脂滴。结果通过分析GSE43292数据发现,Plin2、LOX1在颈动脉粥样硬化斑块中的表达显著高于颈动脉邻近组织。oxLDL处理RAW264.7细胞24 h后,Plin2与LOX1的表达、细胞内脂滴明显增加。过表达Plin2的细胞中LOX1表达升高;当用oxLDL孵育过表达Plin2的细胞后,LOX1的水平升高更为显著;但在没有oxLDL处理的情况下,敲减Plin2对细胞内LOX1的表达没有影响。基因集富集分析(gene set enrichment analysis,GSEA)结果显示,在动脉粥样硬化中,Plin2和LOX1的表达与NF-κB的活化呈正相关。此外,尽管采用oxLDL处理细胞,NF-κB抑制剂JSH-23预处理仍可显著降低Plin2与LOX1的表达、细胞内的脂质积聚,过表达Plin2后,JSH-23亦能显著抑制oxLDL孵育的细胞中Plin2和LOX1的表达。结论Plin2可通过上调LOX1的表达促进细胞内脂质积聚,参与动脉粥样硬化,这一过程至少部分是通过激活NF-κB通路实现的。
文摘We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on LDL receptor gene expression in a human hepatoma cell line (HepG2) treated with Dai-saiko-to extract and the extracts of eight herbs presented in Dai-saiko-to. Dai-saiko-to extract significantly increased LDL receptor gene and SREBP2 gene expression compared with the control. The extracts of four herbs, Bupleurum root, Pinellia tuber, Scutellaria root and Peony root significantly increased the LDL receptor gene expression. Whereas, Jujube, Immature orange, Ginger and Rhubarb extracts did not change the gene expression. These results suggest that Dai-saiko-to increased the expression of the cholesterol transport gene (LDL receptor) regulated by SREBP2 gene in the human hepatoma cell line. The pharmacological activity of Dai-saiko-to against hypercholesterolemia and atheromatous lesions related for these four herbal components.
