Altered lipid synthesis in type II pneumonocytes exposed to lung surfactant.

Altered lipid synthesis in type II pneumonocytes exposed to lung surfactant.
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暴露于肺表面活性剂的 II 型肺细胞中脂质合成发生改变。

DOI:
10.1042/bj2400679
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发表时间:
1986
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
Bleasdale,JE
Bleasdale,JE
中科院分区:
--
文献类型:
--
作者:
Thakur,NR;Tesan,M;Tyler,NE;Bleasdale,JE

文献摘要

被引文献

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当II型肺细胞暴露于含有1-棕榈酰-2-[3 H]棕榈酰-甘油-3-磷酸胆碱的纯化肺表面活性剂时,放射性标记的表面活性剂显然被细胞吸收,因为它不能通过重复洗涤或与非放射性标记的表面活性剂交换而被除去,但当细胞裂解时释放。暴露于[3 H]表面活性剂4小时后,细胞内超过一半的3 H仍以二饱和磷脂酰胆碱的形式存在。掺入[3 H]胆碱,[14 C]棕榈酸和[14 C]乙酸甘油磷脂减少在II型细胞暴露于表面活性剂和这种抑制,如表面活性剂的摄取,是半最大时,细胞外浓度的表面活性剂约。0.1μ mol脂质P/ml。表面活性剂对放射性标记前体掺入的抑制作用发生迅速且可逆,并不仅仅是由于细胞内前体的比放射性稀释。二羟丙酮磷酸酰基转移酶的活性,但不是甘油-3-磷酸酰基转移酶,在II型细胞暴露于表面活性剂,这是反映了在14 C/3 H比的总脂质合成的细胞与[U-14 C]甘油和[2- 3 H]甘油孵育时,暴露于表面活性剂的减少。磷脂酰胆碱,磷脂酰甘油和胆固醇,无论是单独或混合在表面活性剂中发现的摩尔比,没有模仿纯化的表面活性剂在甘油磷脂合成的抑制。与此相反,从表面活性剂分离的载脂蛋白馏分大大抑制[3 H]胆碱掺入脂质和这种抑制活性是不稳定的热和胰蛋白酶。它的结论是,表面活性剂的表观摄取II型细胞在体外是伴随着通过一种机制,涉及表面活性剂脱辅基蛋白的甘油磷脂合成的抑制。
When type II pneumonocytes were exposed to purified lung surfactant that contained 1-palmitoyl-2-[3H]palmitoyl-glycero-3-phosphocholine, radiolabelled surfactant was apparently taken up by the cells since it could not be removed by either repeated washing or exchange with non-radiolabelled surfactant, but was released when the cells were lysed. After 4 h of exposure to [3H]surfactant, more than half of the 3H within cells remained in disaturated phosphatidylcholine. Incorporation of [3H]choline, [14C]palmitate and [14C]acetate into glycerophospholipids was decreased in type II cells exposed to surfactant and this inhibition, like surfactant uptake, was half-maximal when the extracellular concentration of surfactant was approx. 0.1 mumol of lipid P/ml. Inhibition of incorporation of radiolabelled precursors by surfactant occurred rapidly and reversibly and was not due solely to dilution of the specific radioactivity of intracellular precursors. Activity of dihydroxyacetone-phosphate acyltransferase, but not glycerol-3-phosphate acyltransferase, was decreased in type II cells exposed to surfactant and this was reflected by a decrease in the 14C/3H ratio of total lipids synthesized when cells incubated with [U-14C]glycerol and [2-3H]glycerol were exposed to surfactant. Phosphatidylcholine, phosphatidylglycerol and cholesterol, either individually or mixed in the molar ratio found in surfactant, did not mimic purified surfactant in the inhibition of glycerophospholipid synthesis. In contrast, an apoprotein fraction isolated from surfactant inhibited greatly the incorporation of [3H]choline into lipids and this inhibitory activity was labile to heat and to trypsin. It is concluded that the apparent uptake of surfactant by type II cells in vitro is accompanied by an inhibition of glycerophospholipid synthesis via a mechanism that involves a surfactant apoprotein.