Identification of functions of peroxisome proliferator-activated receptor α in proximal tubules
Identification of functions of peroxisome proliferator-activated receptor α in proximal tubules
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DOI：
10.1097/01.asn.0000018403.61042.56
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发表时间：
2002-07-01
影响因子：
13.6
通讯作者：
Aoyama, T
中科院分区：
文献类型：
--
作者：
Kamijo, Y;Hora, K;Aoyama, T
过氧化物酶体增殖物激活受体α（PPARα）是类固醇/核受体超家族的成员，在肾脏中大量表达，但其生理功能尚不清楚。在这项研究中，使用 PPARα 缺失的小鼠来帮助阐明其功能。研究发现，饥饿的 PPARα 缺失小鼠比饥饿的野生型小鼠分泌更多的尿白蛋白。此外，仅在饥饿的PPARα缺失小鼠的近端肾小管中发现巨大溶酶体的出现、白蛋白的显着积累以及白蛋白消化能力受损。这些异常可能是由于饥饿引起的碳水化合物代谢下降和 PPARα 依赖性脂肪酸代谢缺乏而导致 ATP 不足。有趣的是，当给予葡萄糖时，这些异常现象消失了。总而言之，这些发现证明了 PPARα 在近曲小管中的重要功能，通过维持 ATP 稳态来动态调节蛋白质降解系统，并强调了脂肪酸代谢在肾脏生理学中的重要性。
Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the steroid/nuclear receptor superfamily that is intensively expressed in the kidney, but its physiologic function is unknown. In this study, PPARalpha-null mice were used to help clarify the function. Starved PPARalpha-null mice were found to secrete significantly more quantities of urine albumin than starved wild-type mice. Furthermore, the appearance of giant lysosomes, marked accumulation of albumin, and an impaired ability concerning albumin digestion were found only in proximal tubules of the starved PPARalpha-null mice. These abnormalities were probably derived from ATP insufficiency as a result of the starvation-induced decline of carbohydrate metabolism and a lack of PPARalpha-dependent fatty acid metabolism. It is interesting that these abnormalities disappeared when glucose was administered. Taken together, these findings demonstrate important functions of PPARalpha in the proximal tubules, the dynamic regulation of the protein-degradation system through maintenance of ATP homeostasis, and emphasize the importance of the fatty acid metabolism in renal physiology.