Skeletal muscle regeneration and oxidative stress are altered in chronic kidney disease

Keith G. Avin, Xuening (Neal) Chen, Jason Organ, Chad Zarse, Kalisha O'Neill, Richard G. Conway, Robert J. Konrad, Robert Bacallao, Matthew Allen, Sharon Moe

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Skeletal 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.

Original languageEnglish (US)
Article numbere0159411
JournalPLoS One
Volume11
Issue number8
DOIs
StatePublished - Aug 1 2016

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Oxidative stress
muscle development
kidney diseases
Chronic Renal Insufficiency
Muscle
skeletal muscle
Regeneration
Skeletal Muscle
Oxidative Stress
oxidative stress
Myostatin
myostatin
Rats
Muscles
muscles
succinate dehydrogenase (quinone)
Animals
Myogenin
muscular atrophy
Mitochondria

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Skeletal muscle regeneration and oxidative stress are altered in chronic kidney disease. / Avin, Keith G.; Chen, Xuening (Neal); Organ, Jason; Zarse, Chad; O'Neill, Kalisha; Conway, Richard G.; Konrad, Robert J.; Bacallao, Robert; Allen, Matthew; Moe, Sharon.

In: PLoS One, Vol. 11, No. 8, e0159411, 01.08.2016.

Research output: Contribution to journalArticle

Avin, Keith G. ; Chen, Xuening (Neal) ; Organ, Jason ; Zarse, Chad ; O'Neill, Kalisha ; Conway, Richard G. ; Konrad, Robert J. ; Bacallao, Robert ; Allen, Matthew ; Moe, Sharon. / Skeletal muscle regeneration and oxidative stress are altered in chronic kidney disease. In: PLoS One. 2016 ; Vol. 11, No. 8.
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