Reduction of mitochondria and up regulation of pyruvate dehydrogenase kinase 4 of skeletal muscle in patients with chronic kidney disease

作者：Chenqi Xu, Ayijiaken Kasimumali, Xiangjiang Guo, Renhua Lu, Kewei Xie, Mingli Zhu, Yingying Qian, Xiaohuan Chen, Huihua Pang, Qin Wang, Zhuping Fan, Huili Dai, Shan Mou, Zhaohui Ni, Leyi Gu · 发表于：Nephrology · 年份：2019 · DOI：10.1111/nep.13606 · 被引用次数：28 · 研究领域：Dialysis and Renal Disease Management、Biochemical Acid Research Studies、Mitochondrial Function and Pathology

AIM: Muscle weakness is commonly among chronic kidney disease (CKD) patients. Muscle mitochondrial dysfunction and decreased pyruvate dehydrogenase (PDH) activity occur in CKD animals but have not been confirmed in humans, and changes in pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) expression have not been evaluated in CKD muscle. We presume that the reduction of muscle mitochondria and post-translational modification of PDH may cause muscle weakness in CKD patients. Herein, we explored changes in mitochondrial morphology, PDH expression and activity, and PDK/PDP expression in CKD patient muscle. METHODS: Twenty patients with stage 4-5 CKD (CKD group) and 24 volunteers (control group) were included. Clinical characteristics, biochemical information and handgrip strength (HGS) were determined. Skeletal muscle samples were collected from eight stage 5 CKD patients from CKD group. Other eight non-CKD surgical subjects' muscle samples were collected as control. PDH activity was determined using a PDH enzyme activity assay kit, and real-time PCR and western blotting analyses were performed to measure gene expression and protein levels, respectively. Transmission electron microscopy was used to study mitochondria morphology. RESULTS: CKD patients had lower HGS than non-CKD subjects, and HGS was correlated with gender, age, haemoglobin and albumin. Mitochondria were decreased in end-stage renal disease (ESRD) patients muscle. Mfn-1 expression and ...