Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease

dc.contributor.authorAvin, Keith G.
dc.contributor.authorChen, Neal X.
dc.contributor.authorOrgan, Jason M.
dc.contributor.authorZarse, Chad
dc.contributor.authorO'Neil, Kalisha
dc.contributor.authorConway, Richard G.
dc.contributor.authorKonrad, Robert J.
dc.contributor.authorBacallao, Robert L.
dc.contributor.authorAllen, Matthew R.
dc.contributor.authorMoe, Sharon M.
dc.contributor.departmentDepartment of Physical Therapy, School of Health and Rehabilitation Sciencesen_US
dc.date.accessioned2017-06-07T20:22:55Z
dc.date.available2017-06-07T20:22:55Z
dc.date.issued2016-08-03
dc.description.abstractSkeletal muscle atrophy and impaired muscle function are associated with lower health-related quality of life, and greater disability and mortality risk in those with chronic kidney disease (CKD). However, the pathogenesis of skeletal dysfunction in CKD is unknown. We used a slow progressing, naturally occurring, CKD rat model (Cy/+ rat) with hormonal abnormalities consistent with clinical presentations of CKD to study skeletal muscle signaling. The CKD rats demonstrated augmented skeletal muscle regeneration with higher activation and differentiation signals in muscle cells (i.e. lower Pax-7; higher MyoD and myogenin RNA expression). However, there was also higher expression of proteolytic markers (Atrogin-1 and MuRF-1) in CKD muscle relative to normal. CKD animals had higher indices of oxidative stress compared to normal, evident by elevated plasma levels of an oxidative stress marker, 8-hydroxy-2' -deoxyguanosine (8-OHdG), increased muscle expression of succinate dehydrogenase (SDH) and Nox4 and altered mitochondria morphology. Furthermore, we show significantly higher serum levels of myostatin and expression of myostatin in skeletal muscle of CKD animals compared to normal. Taken together, these data show aberrant regeneration and proteolytic signaling that is associated with oxidative stress and high levels of myostatin in the setting of CKD. These changes likely play a role in the compromised skeletal muscle function that exists in CKD.en_US
dc.identifier.citationAvin, K. G., Chen, N. X., Organ, J. M., Zarse, C., O’Neill, K., Conway, R. G., … Moe, S. M. (2016). Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease. PLoS ONE, 11(8), e0159411. http://doi.org/10.1371/journal.pone.0159411en_US
dc.identifier.urihttps://hdl.handle.net/1805/12903
dc.language.isoen_USen_US
dc.publisherPlosen_US
dc.relation.isversionof10.1371/journal.pone.0159411en_US
dc.relation.journalPLoS ONEen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/
dc.sourcePMCen_US
dc.subjectMusclesen_US
dc.subjectSkeletal musclesen_US
dc.subjectAtrophyen_US
dc.subjectChronic kidney diseaseen_US
dc.subjectSkeletal dysfunctionen_US
dc.titleSkeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Diseaseen_US
dc.typeArticleen_US
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