{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:19:02Z","timestamp":1790363942896,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T00:00:00Z","timestamp":1497225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI 16H05114"],"award-info":[{"award-number":["KAKENHI 16H05114"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS\u2010targeted intervention using AST\u2010120, which inhibits IS accumulation, or mitochondria\u2010targeted intervention using L\u2010carnitine or teneligliptin, a dipeptidyl peptidase\u20104 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>in vitro<\/jats:italic>\n                      effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5\/6\u2010nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non\u2010treatment group and AST\u2010120, L\u2010carnitine, or teneligliptin treatment groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC\u20101\u03b1 and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co\u2010incubation with an anti\u2010oxidant, ascorbic acid, L\u2010carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin\u20106 and atrophy\u2010related factors such as myostatin and atrogin\u20101 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG\u20101\u03b1 and increased muscular autophagy, as reflected by decreased mitochondria\u2010rich type I fibres. An AST\u2010120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L\u2010carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS\u2010targeted and mitochondria\u2010targeted interventions for treating CKD\u2010induced muscle atrophy and decreased exercise endurance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12202","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T22:32:39Z","timestamp":1497306759000},"page":"735-747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":156,"title":["Potential therapeutic interventions for chronic kidney disease\u2010associated sarcopenia\n                    <i>via<\/i>\n                    indoxyl sulfate\u2010induced mitochondrial dysfunction"],"prefix":"10.1002","volume":"8","author":[{"given":"Yuki","family":"Enoki","sequence":"first","affiliation":[{"name":"Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Center for Clinical Pharmaceutical Sciences, School of Pharmacy Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riho","family":"Arake","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences Kumamoto University  Kumamoto 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