Gentamicin-induced alterations in phospholipid metabolism in cultured human proximal tubular cells.
Gentamicin-induced alterations in phospholipid metabolism in cultured human proximal tubular cells.
复制标题
庆大霉素诱导培养的人近端肾小管细胞中磷脂代谢的改变。
DOI：
10.1002/jbt.2570020304
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Chatterjee,S
中科院分区：
文献类型：
--
作者：
Chatterjee,S
观察庆大霉素对体外培养的人近端肾小管上皮细胞磷脂水平和代谢的影响，以及低密度脂蛋白(LDL)对磷脂酰胆碱(PC)摄取的影响。与对照细胞相比，与庆大霉素(0.3 mM)孵育1-21天的细胞数量和蛋白质有相似的增加。然而，磷脂酰胆碱(PC)和鞘磷脂(SM)的细胞水平呈时间依赖性增加，而其他磷脂则不增加。庆大霉素(0.3~3.0 mM)可使PC(50%~320%)和SM(20%~40%)水平呈浓度依赖性增加，庆大霉素可促进[14C]-乙酸酯分别掺入甘油二酯、PC和SM，分别为300%、66%和20%，但对溶血磷脂酰胆碱(LPC)无明显影响。同样，与对照细胞相比，庆大霉素对PC和SM的[14C]-胆碱掺入的刺激作用分别为300%和172%，但对LPC的掺入作用不明显。此外，庆大霉素还能刺激胞苷二磷胆碱(CDP-胆碱)掺入[14C]-胆碱。然而，庆大霉素孵育的细胞吞噬[14C]-PC-LDL的能力低于对照细胞。因此，在与庆大霉素孵育的PT细胞中，外源来源的低密度脂蛋白并不导致PC水平的增加。在与庆大霉素孵育的细胞中，胞苷三磷酸(CTP)：磷酸胆碱胞苷转移酶的活性略低于对照组。相比之下，与庆大霉素共同孵育21天的细胞中，磷脂酶A1和磷脂酶C的活性比对照组低两倍。因此，在与庆大霉素孵育的细胞中，[14C]-乙酸酯和[14C]-胆碱掺入PC的增加可能不仅是由于内源性合成的增加，而且是由于新合成的PC分解代谢的减少。我们的结论是，庆大霉素损害PC的溶酶体分解代谢，导致其在PT细胞中积聚。这一现象可能是庆大霉素引起的人类肾毒性的一种迹象。
The effects of gentamicin on phospholipid levels and metabolism and the uptake of phosphatidylcholine (PC) adsorbed to low‐density lipoprotein (LDL) were investigated in cultured human proximal tubular (PT) cells. Cells incubated with gentamicin (0.3 mM) for one to 21 days had a similar increase in the cell number and protein as compared to control cells. However, the cellular levels of phosphatidylcholine (PC) and sphingomyelin (SM), but not other phospholipids, increased in a time‐dependent manner. Incubation of gentamicin (0.3 to 3.0 mM) resulted in a concentration‐dependent increase in the cellular levels of PC (50% to 320%) and SM (20% to 40%).Gentamicin stimulated the incorporation of [14C]‐acetate into diacylglycerol, PC, and SM in the order of 300%, 66%, and 20%, respectively, but not into lysophosphatidylcholine (LPC). Similarly, gentamicin stimulated the incorporation of [14C]‐choline into PC and SM in the order of 300% and 172%, respectively, but not into LPC as compared to control cells. In addition, gentamicin also stimulated the incorporation of [14C]‐choline into cytidine diphosphocholine (CDP‐choline). However, the endocytosis of [14C]‐PC‐LDL was lower in cells incubated with gentamicin than in control cells. Thus, exogenously derived PC on LDL does not contribute to the increased cellular levels of PC in PT cells incubated with gentamicin.The activity of cytidine triphosphate (CTP):phosphocholine cytidyltransferase was moderately lower in cells incubated with gentamicin as compared to control. By contrast, the activity of phospholipase A1and phospholipase C was twofold lower in cells incubated with gentamicin for 21 days as compared to control. Thus, increased incorporation of [14C]‐acetate and [14C]‐choline into PC in cells incubated with gentamicin may not only be due to increased endogenous synthesis but to decreased catabolism of newly synthesized PC. We conclude that gentamicin impairs the lysosomal catabolism of PC, leading to its accumulation in PT cells. This phenomenon may be an indication of gentamicin‐induced nephrotoxicity in man.