Transcriptional regulation of intracellular cholesterol metabolism

细胞内胆固醇代谢的转录调控

• 批准号: 07557161
• 负责人: TAKANO Tatsuya
• 金额: $ 9.66万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557161/
• 关键词: Cholesterol; LDL Receptor; SREBP; Transcription; Atherosclerosis; HMGCoA合成酵素; 高脂血症; SRE; 転写調節; ALLN; LDL受容体転写因子; HMGCoA還元酵素; コレステロール合成

Animal cells synthesize cholesterol from acetyl CoA through a series of more than 20 enzymatic reactions. In addition, cells obtain cholesterol from plasma in the form of lowdensity lipoprotein (LDL), which is internalized via the LDL receptor and hydrolyzed to free cholesterol in lysosomes. Each cell must balance these internal and external sources while avoiding sterol shortage or over-accunrulation. Both the biosynthetic and uptake pathways are well-regulated through feedback control. When cells are cultured in the presence of LDL,the activity of both 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase and HMG CoA reductase decline by more than 90% and the number of LDL receptors also decreases. In the absence of LDL,the cells maintain high activities of these two enzymes, which are rate-limiting enzymes of the biosynthetic pathway, and also maintain a large number of LDL receptors on their surface. We assess recent progress in understanding the mechanisms involved in transcriptional and posttranscriptional regulation of intracellular cholesterol metabolism.

动物细胞通过20多种酶促反应从乙酰辅酶A合成胆固醇。此外，细胞从血浆中获得低密度脂蛋白（LDL）形式的胆固醇，其通过LDL受体内化并在溶酶体中水解为游离胆固醇。每个细胞必须平衡这些内部和外部来源，同时避免固醇短缺或过度积累。生物合成和摄取途径都通过反馈控制得到良好调节。当细胞在LDL存在下培养时，3-羟基-3-甲基戊二酰辅酶A（HMG CoA）合酶和HMG CoA还原酶的活性下降超过90%，LDL受体的数量也减少。在不存在LDL的情况下，细胞保持这两种酶的高活性，这两种酶是生物合成途径的限速酶，并且还在其表面上保持大量LDL受体。我们评估最近的进展，了解在转录和转录后调节细胞内胆固醇代谢的机制。

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