Effect of gentamicin on phospholipid metabolism in cultured rabbit proximal tubular cells.
Effect of gentamicin on phospholipid metabolism in cultured rabbit proximal tubular cells.
复制标题
庆大霉素对培养兔近端肾小管细胞磷脂代谢的影响。
DOI：
10.1152/ajpcell.1989.256.1.c204
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Kaloyanides,GJ
中科院分区：
文献类型：
--
作者：
Ramsammy,LS;Josepovitz,C;Lane,B;Kaloyanides,GJ
我们验证了一种假设，即暴露于庆大霉素的细胞中磷脂的积累是由于受损的降解所致。实验在原代培养的兔近端肾小管上皮细胞上进行。10(-3)M庆大霉素组细胞呈髓样小体形成，总磷脂逐渐增多，第6天较对照组增加44%，其中磷脂酰肌醇增加235%，磷脂酰胆碱增加60%，磷脂酰乙醇胺增加90%，磷脂酰丝氨酸增加55%。庆大霉素可抑制这些磷脂的降解。[~3H]肌醇标记的磷脂池的t1/2从1.17天增加到2.88天(庆大霉素组)，[~H]胆碱池的t1/2从1.77天增加到2.38天，[3H]乙醇胺池的t1/2从3.14天增加到4.93天，[~3H]丝氨酸池的t1/2从6.30天增加到8.63天，t1/2增加了146%。细胞暴露于庆大霉素2天后，[~3H]肌醇(68%)和[~3H]乙醇胺(59%)对磷脂的掺入也增加。这些数据与庆大霉素抑制溶酶体磷脂酶活性的假设是一致的，溶酶体磷脂酶活性导致磷脂在溶酶体内以髓样体的形式积聚。磷脂合成增加可能是对受损的磷脂溶酶体降解的一种代偿反应。我们推测，磷脂酰肌醇的优先增加反映了多阳离子庆大霉素与阴离子磷脂酰肌醇静电相互作用并抑制其周转的能力。
We examined the hypothesis that the accumulation of phospholipid in cells exposed to gentamicin is due to impaired degradation. Experiments were performed in rabbit proximal tubular cells grown in primary culture. Cells exposed to 10(-3) M gentamicin manifested myeloid body formation and a progressive increase in total phospholipid that by day 6 was 44% higher than that of control cells and reflected increases of phosphatidylinositol of 235%, phosphatidylcholine of 60%, phosphatidylethanolamine of 90%, and phosphatidylserine of 55% above control values. Gentamicin impaired the degradation of these phospholipids. The t1/2 of the phospholipid pool labeled with [3H]myoinositol increased 146% from 1.17 (control) to 2.88 days (gentamicin); the t1/2 of the [3H]choline pool increased 34% from 1.77 to 2.38 days; the t1/2 of the [3H]ethanolamine pool increased 57% from 3.14 to 4.93 days; the t1/2 of the [3H] serine pool increased 37% from 6.30 to 8.63 days. Exposure of cells to gentamicin for 2 days also stimulated increased incorporation of [3H]myoinositol (68%) and [3H]ethanolamine (59%) into phospholipid. The data are consistent with the hypothesis that gentamicin inhibits the activity of lysosomal phospholipases that results in the accumulation of phospholipid within the lysosome in the form of myeloid bodies. Increased phospholipid synthesis may represent a compensatory response to the impaired lysosomal degradation of phospholipid. We postulate that the preferential increase of phosphatidylinositol reflects the capacity of the polycationic gentamicin to interact electrostatically with the anionic phosphoinositides and inhibit their turnover.