Hepatic alpha 2 mu-globulin: a potential metabolic role in the rat proximal tubule.
Hepatic alpha 2 mu-globulin: a potential metabolic role in the rat proximal tubule.
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肝 α2 mu 球蛋白：在大鼠近曲小管中的潜在代谢作用。
DOI：
10.1152/ajprenal.1996.271.3.f527
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Schwartz,JH
中科院分区：
文献类型：
--
作者：
Borkan,SC;Wang,YH;Lam,KT;Brecher,P;Schwartz,JH
在本研究中，我们提供了免疫组化和免疫证据本地化丰富，15.5 kDa的蛋白质的可溶性蛋白质部分的近端小管。这种15.5-kDa蛋白在体外结合脂肪酸，并与α 2 μ-球蛋白（A2片段）的氨基酸10-117具有同一性，α 2 μ-球蛋白是一种主要在雄性肝脏中合成的19-kDa蛋白。用逆转录-聚合酶链反应，在雄性肝脏中检测到A2的mRNA，但在雄性肾脏中未检测到。在静脉注射纯化的19-kDa蛋白（A2）的雌性大鼠肾皮质中观察到15.5-kDa蛋白的从头蓄积，表明较大蛋白的肾内加工。这种蛋白质在近端小管，一个网站，利用脂肪酸作为一个重要的代谢底物的潜在作用，确定在隔离的近端小管段。脂肪酸和葡萄糖氧化率在三个实验模型中测定，其中15.5 kDa蛋白质几乎不存在：1）用醋酸脱氧皮质酮和盐处理的单侧肾切除雄性大鼠，2）双侧肾上腺切除的雄性大鼠，和3）正常雌性大鼠。在没有15.5 kDa蛋白的情况下，脂肪酸氧化速率降低了30- 55%，而葡萄糖氧化在所有三种模型中均显著增加。在女性肾皮质中，15.5 kDa蛋白质的消耗与心脏脂肪酸结合蛋白（一种脂肪酸的替代细胞内转运蛋白）的升高相关。这些数据支持肝α 2 μ球蛋白的蛋白水解裂解产物可能促进近端小管中油酸盐（一种疏水配体）的氧化的假设。
In the present study, we provide immunohistochemical and immunologic evidence to localize an abundant, 15.5-kDa protein to the soluble protein fraction of the proximal tubule. This 15.5-kDa protein binds fatty acids in vitro and has identity with amino acids 10-117 of alpha 2 mu-globulin (A2 fragment), a 19-kDa protein synthesized predominantly in the male liver. With reverse transcription-polymerase chain reaction, mRNA for A2 was detected in male liver but not in the male kidney. De novo accumulation of the 15.5-kDa protein was observed in the renal cortex of female rats given intravenous injections of purified 19-kDa protein (A2), suggesting intrarenal processing of the larger protein. The potential role of this protein in the proximal tubule, a site that utilizes fatty acids as an important metabolic substrate, was determined in isolated proximal tubule segments. Fatty acid and glucose oxidation rates were measured in three experimental models in which the 15.5-kDa protein was virtually absent: 1) uninephrectomized male rats treated with deoxycorticosterone acetate and salt, 2) male rats subjected to bilateral adrenalectomy, and 3) normal female rats. In the absence of the 15.5-kDa protein, fatty acid oxidation rates decreased by 30-55%, whereas glucose oxidation significantly increased in all three models. In female renal cortex, depletion of the 15.5-kDa protein was associated with a rise in heart fatty acid binding protein, an alternative intracellular transporter of fatty acids. These data support the hypothesis that a proteolytic cleavage product of hepatic alpha 2 mu-globulin may facilitate the oxidation of oleate, a hydrophobic ligand, in the proximal tubule.