Correlation between two effects of high density lipoproteins on vascular endothelial cells. The induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and the support of cellular proliferation.
Correlation between two effects of high density lipoproteins on vascular endothelial cells. The induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and the support of cellular proliferation.
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DOI：
10.1016/s0021-9258(18)34088-2
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发表时间：
1982-08
期刊：
影响因子：
--
通讯作者：
D. Cohen;S. Massoglia;D. Gospodarowicz
中科院分区：
文献类型：
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作者：
D. Cohen;S. Massoglia;D. Gospodarowicz
人高密度脂蛋白（HDL）是一种对牛血管内皮细胞有丝分裂作用的异质性颗粒，可刺激3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶活性，该活性存在于活跃增殖的稀疏内皮细胞和非分裂融合培养物中。在融合细胞中研究了酶对HDL的反应动力学，并在稀疏细胞中研究了还原酶活性与增殖之间的关系。在汇合细胞中，HMG-CoA还原酶具有1- 2pmol/min/10 - 7细胞的稳定基础活性。HDL的酶诱导是浓度依赖性的（25-1000 pg HDL蛋白/ml）和时间依赖性的（3小时内可检测到，2-4天稳定上升）。最佳刺激导致酶水平增加10倍。HDL亚组分（密度1.130-1.21 μ g/ml）是比HDLz亚组分（密度1.07-1.125 μ g/ml）更有效的刺激剂。低密度脂蛋白（LDL）阻止和逆转对HDL的酶反应。活跃分裂细胞的HMG-CoA还原酶比活性是静止融合细胞的50倍，并随着细胞密度的增加而逐渐降低。相对于增殖细胞的基线活性下降，观察到酶活性的HDL刺激和LDL抑制。细胞暴露于一种还原酶抑制剂compactin，停止分裂并死亡。然而，暴露于HDL的生长细胞比暴露于LDL的细胞对压缩蛋白毒性的抵抗力高10倍。因此，细胞增殖似乎更依赖于HMG-CoA还原酶的活性，而不是胆固醇（由LDL提供）的可用性。LDL确实增加HDL支持的增殖速率。类似地，HDLz（其可以LDL样方式通过apo-E提供一些胆固醇）是比HDL 3更有效的促有丝分裂剂，但是还原酶的有效刺激剂较低。
Human high density lipoproteins (HDLs), a heterogeneous class of particles which is mitogenic for bovine vascular endothelial cells, stimulate the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity present in both actively proliferating sparse endothelial cells and in nondividing confluent cultures. Kinetics of the enzyme response to HDLs was studied in confluent cells, and the relationship between reductase activity and proliferation was examined in sparse cells. In confluent cells, HMG-CoA reductase has a stable basal activity of 1-2 pmol/min/lO ‘cells. The enzyme induction by HDLs is concentration-dependent (25-1000 pg of HDL protein/ml) and time-dependent (detectable within 3 h, rising steadily for 2-4 days). Optimal stimulation resulted in a 10-fold increase in the enzyme levels. The HDL, subfraction (density 1.130-1.21 g/ml) is a more potent stimulator than HDLz subfraction (density 1.07-1.125 g/ml). Low density lipoprotein (LDL) prevents and reverses the enzyme response to HDLs.The HMG-CoA reductase specific activity of actively dividing cells is 50-fold that of quiescent confluent cells and progressively decreases as cell density increases. Against the falling base-line activity of proliferating cells, both an HDL stimulation and an LDL inhibition of enzyme activity are seen. Cells exposed to compactin, a reductase inhibitor, stop dividing and die. Growing cells exposed to HDLs, however, are 10-fold more resistant to compactin toxicity than cells exposed to LDL. Cell proliferation thus appears to be more dependent on the activity of HMG-CoA reductase than on the availability of cholesterol (as provided by LDL). LDL does increase the rate of proliferation supported by HDLs. Similarly, HDLz (which may donate some cholesterol via apo-E, in an LDL-like manner) is a more potent mitogen, but less effective stimulator of reductase, than HDL3.