Uremic Myopathy and Mitochondrial Dysfunction in Kidney Disease.
Uremic Myopathy and Mitochondrial Dysfunction in Kidney Disease.
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DOI：
10.3390/ijms232113515
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发表时间：
2022-11-04
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
慢性肾病（CKD）患者肌肉结构和功能的改变与不良预后相关。作为肌肉细胞稳态的关键细胞器，线粒体代谢已在 CKD 肌肉功能障碍的背景下进行了研究。我们进行了一项研究，以确定氧化代谢、糖酵解和脂肪酸氧化对 CKD 肌肉代谢的贡献。小鼠因摄入饮食中的腺嘌呤而患上慢性肾病。与非 CKD 小鼠相比，CKD 小鼠的肌肉体重明显减轻，但只有趾长伸肌 (EDL) 的纤维数量减少。 CKD 和非 CKD 小鼠的各种肌纤维的比例没有差异。 CKD 小鼠的肌肉中与氧化磷酸化相关的蛋白质表达减少，但与糖酵解相关的酶和转运蛋白表达增加。在细胞培养中，暴露于尿毒症血清的肌管在使用葡萄糖作为底物时表现出降低的耗氧率（OCR），在使用脂肪酸时表现出保守的OCR并且增加了乳酸的产生。总之，腺嘌呤诱导的 CKD 小鼠出现肌肉减少症，糖酵解代谢增加，但纤维结构没有明显变化。尿毒症肌病的体外模型表明，与葡萄糖利用减少相比，脂肪酸利用得以保留。
Alterations in muscle structure and function in chronic kidney disease (CKD) patients are associated with poor outcomes. As key organelles in muscle cell homeostasis, mitochondrial metabolism has been studied in the context of muscle dysfunction in CKD. We conducted a study to determine the contribution of oxidative metabolism, glycolysis and fatty acid oxidation to the muscle metabolism in CKD. Mice developed CKD by exposure to adenine in the diet. Muscle of CKD mice showed significant weight loss compared to non-CKD mice, but only extensor digitorum longus (EDL) muscle showed a decreased number of fibers. There was no difference in the proportion of the various muscle fibers in CKD and non-CKD mice. Muscle of CKD mice had decreased expression of proteins associated with oxidative phosphorylation but increased expression of enzymes and transporters associated with glycolysis. In cell culture, myotubes exposed to uremic serum demonstrated decreased oxygen consumption rates (OCR) when glucose was used as substrate, conserved OCR when fatty acids were used and increased lactate production. In conclusion, mice with adenine-induced CKD developed sarcopenia and with increased glycolytic metabolism but without gross changes in fiber structure. In vitro models of uremic myopathy suggest fatty acid utilization is preserved compared to decreased glucose utilization.
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影响因子：
4.2
作者：
Chu, Nadia M.;Chen, Xiaomeng;McAdams-DeMarco, Mara A.
通讯作者：
McAdams-DeMarco, Mara A.
DOI：
10.2215/cjn.10320819
发表时间：
2020-07-01
影响因子：
9.8
作者：
Gamboa, Jorge L.;Roshanravan, Baback;Ikizler, T. Alp
通讯作者：
Ikizler, T. Alp
影响因子：
1.7
作者：
Filiopoulos, Vassilis;Hadjiyannakos, Dimitrios;Vlassopoulos, Dimosthenis
通讯作者：
Vlassopoulos, Dimosthenis
一种不依赖于阳离子的甘露糖 6-磷酸受体抑制剂 (PXS64) 通过抑制转化生长因子-β1 的激活来改善肾纤维化。
影响因子：
3.7
作者：
Zhang J;Wong MG;Wong M;Gross S;Chen J;Pollock C;Saad S
通讯作者：
Saad S
影响因子：
1.6
作者：
Johansen, Kirsten L.;Delgado, Cynthia;Tamura, Manjula Kurella
通讯作者：
Tamura, Manjula Kurella