通过增加低密度脂蛋白受体表达,降低低密度脂蛋白胆固醇
Marjolein A W van den Boogert1,2, Lars E Larsen2,3, Lubna Ali2
1Departments of Vascular Medicine (M.A.W.v.d.B., J.K., G.M.D.-T., E.S.G.S., A.G.H.), Amsterdam University Medical Centers, location AMC, The Netherlands.
Circulation
|May 24, 2019
概括
缺陷的N-糖化在先天性糖化乱 (CDG) 导致增加的LDL受体活性和胆固醇清除. 这表明向N-糖化可能提供降低LDL胆固醇和心血管疾病风险的新疗法.
科学领域:
- 生物化学
- 遗传学
- 代谢疾病
背景情况:
- 蛋白质糖化在调节脂质代谢中起着至关重要的作用.
- 遗传性糖化失调 (CDG) 涉及蛋白质糖化中的缺陷.
- I型CDG特别影响N-糖化途径.
研究的目的:
- 研究N-糖化缺陷对脂质代谢的影响.
- 研究1型CDG患者,重点研究ALG6和PMM2缺乏.
- 在这些患者中探索调节低密度脂蛋白 (LDL) 代谢的机制.
主要方法:
- 研究了29名患有ALG6或PMM2缺乏症的CDG患者和23名异质合体的亲属.
- 使用细胞模型 (HepG2,患者纤维细胞,iPSC衍生的肝细胞) 来分析LDL代谢.
- 测量了阿波利波蛋白B,LDL受体表达,LDL吸收,SREBP2激活和ER压力标志物.
主要成果:
- 患有I型CDG的患者表现出低乙醇蛋白血症 (低LDL胆固醇和B类脂质蛋白).
- 由于较高的LDL受体丰度,由于SREBP2表达升高而观察到增加的LDL吸收.
- 临床上未受影响的异质合体亲属也显示LDL- C和Apolipoprotein B水平降低.
结论:
- N- 糖化是LDL代谢的重要调节剂.
- 在LDL途径中准N-糖化是一种降低LDL-C的潜在治疗策略.
- 这种方法可能为预防心血管疾病提供新的治疗方法.
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