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携带脂肪酸的白蛋白对近端肾小管细胞系的代谢影响。

Metabolic effects of fatty acid-bearing albumin on a proximal tubule cell line.

作者信息

Thomas M E, Morrison A R, Schreiner G F

机构信息

Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

出版信息

Am J Physiol. 1995 Jun;268(6 Pt 2):F1177-84. doi: 10.1152/ajprenal.1995.268.6.F1177.

Abstract

In glomerular disease, fatty acids carried on albumin are taken up by the proximal tubule with filtered albumin. We postulate that the fatty acids carried on filtered albumin could contribute to the deleterious effects of proteinuria. The effects of fatty acid-albumin complexes on lipid metabolism have been studied in opossum kidney (OK) cells, a proximal tubule cell line. OK cells transported two-thirds of [14C]palmitate-albumin (5 mg/ml) intracellularly within 16 h. [14C]palmitate-albumin was distributed into phosphatidylcholines, phosphatidylinositols, and tri- and diglycerides. 14C-labeled unsaturated fatty acid albumins (oleate, linoleate, and arachidonate) showed preferential incorporation into triglycerides, with lesser incorporation into phospholipids. Studies of total lipid pools showed that fatty acid-albumin uptake produced a particularly marked increase in total triglyceride levels (approximately 10-fold). Oil red O staining of OK cells cultured with oleate-albumin showed a marked increase in intracellular lipid droplets, compared with cells cultured with delipidated albumin, consistent with triglyceride accumulation. Less than 1% of [14C]palmitate taken up was isolated as intracellular free fatty acid. Less than 5% of [14C]palmitate internalized was oxidized to 14CO2. Different fatty acids, when taken up by the OK cell, have distinct metabolic fates. Each fatty acid is incorporated in a characteristic fashion into certain complex lipids, possibly dependent on the presence or absence of double bonds. We propose that this may have functional consequences for the proximal tubule in the human nephrotic syndrome.

摘要

在肾小球疾病中,与滤过白蛋白结合的脂肪酸会被近端小管与滤过的白蛋白一起摄取。我们推测,滤过白蛋白携带的脂肪酸可能会导致蛋白尿的有害影响。已在负鼠肾(OK)细胞(一种近端小管细胞系)中研究了脂肪酸 - 白蛋白复合物对脂质代谢的影响。OK细胞在16小时内将三分之二的[14C]棕榈酸 - 白蛋白(5mg/ml)转运到细胞内。[14C]棕榈酸 - 白蛋白分布在磷脂酰胆碱、磷脂酰肌醇以及甘油三酯和甘油二酯中。14C标记的不饱和脂肪酸白蛋白(油酸、亚油酸和花生四烯酸)显示优先掺入甘油三酯,而较少掺入磷脂。对总脂质池的研究表明,脂肪酸 - 白蛋白摄取使总甘油三酯水平显著升高(约10倍)。用油酸 - 白蛋白培养的OK细胞的油红O染色显示,与用脱脂白蛋白培养的细胞相比,细胞内脂质滴显著增加,这与甘油三酯积累一致。摄取的[14C]棕榈酸中不到1%被分离为细胞内游离脂肪酸。内化的[14C]棕榈酸中不到5%被氧化为14CO2。不同的脂肪酸被OK细胞摄取后具有不同的代谢命运。每种脂肪酸以特定方式掺入某些复合脂质中,这可能取决于双键的存在与否。我们认为,这可能对人类肾病综合征中的近端小管产生功能性影响。

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