Cholesterol, lipid rafts, and disease
Cholesterol, lipid rafts, and disease
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DOI：
10.1172/jci200216390
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发表时间：
2002-09-01
影响因子：
15.9
通讯作者：
Ehehalt, R
中科院分区：
文献类型：
--
作者：
Simons, K;Ehehalt, R
使用的非标准缩写：糖磷脂酰肌醇锚定(GPI-Anchored)；内皮型一氧化氮合酶(ENOS)；β-分泌酶(BACE)；内质网(ER)；婴儿地鼠肾(BHK)；耐洗涤剂膜(DRM)；阿尔茨海默病(AD)；淀粉样蛋白-β-肽(Aβ)。MA膜。这一增加似乎是通过将脂筏排除在高尔基复合体和ER之间的逆行交通中而实现的(8)。因此，脂筏从高尔基复合体向前移动到质膜，在那里它们浓缩，但也扩散到内吞循环途径(9)。胆固醇和鞘脂的浓度受到严格控制，限制了脂筏对高尔基体细胞器供应的供应。细胞为使用胆固醇作为间隔物将脂筏保持在一起而付出了代价。胆固醇是有毒的，它的细胞水平受到胆固醇生物合成和细胞摄取的转录调控的复杂网络的严格控制，也通过胆固醇以酯化形式沉积到脂肪液滴中，以及通过细胞外流(REF。10；另见Tall等人。11]和Tabas[参考文献12]，本透视系列)。如表1所示，这些严格调控的过程的紊乱会导致各种脂代谢疾病。
Nonstandard abbreviations used: glycophosphatidylinositolanchored (GPI-anchored); endothelial nitric oxide synthase (eNOS); β-secretase (BACE); endoplasmic reticulum (ER); baby hamster kidney (BHK); detergent-resistant membranes (DRMs); Alzheimer disease (AD); amyloid-β-peptide (Aβ). ma membrane. This increase seems to be achieved by excluding lipid rafts from the retrograde traffic between the Golgi complex and the ER (8). Thus, lipid rafts are moved forward from the Golgi complex to the plasma membrane, where they concentrate but also spread into the endocytic recycling pathways (9). Cholesterol and sphingolipid concentrations are tightly regulated and limit the supply of lipid rafts to organelles supplied by the Golgi apparatus.The cell pays a price for using cholesterol as a spacer for keeping rafts together. Cholesterol is toxic, and its cellular levels are kept in tight control by an intricate network of transcriptional regulation of cholesterol biosynthesis and cellular uptake as well as by deposition of cholesterol into fat droplets in an esterified form, and by cellular efflux (ref. 10; see also Tall et al.[ref. 11] and Tabas [ref. 12], this Perspective series). Disturbance of these tightly regulated processes leads to a variety of diseases of lipid metabolism, as shown in Table 1.