Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease

Chang Liu, Eva Karin Gidlund, Anna Witasp, Abdul Rashid Qureshi, Magnus Söderberg, Anders Thorell, Gustavo A. Nader, Peter Barany, Peter Stenvinkel, Ferdinand von Walden

Research output: Contribution to journalArticle

Abstract

Advanced chronic kidney disease (CKD) is characterized by a premature aging phenotype of multifactorial origin. Mitochondrial dysfunction is prevalent in CKD and has been proposed as a major contributor to poor muscle function. Although the mitochondria-derived peptides (MDPs) humanin and mitochondrial open reading frame of 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis, and glucose control, the implications of MDP in CKD are unknown. We investigated humanin and MOTS-c protein expression in skeletal muscle and serum levels in CKD at stage 5 (glomerular filtration rate: <15 ml/min) patients and age-matched controls with normal renal function. Whereas circulating levels of humanin were increased in CKD, local muscle expression was reduced. In contrast, MOTS-c levels were reduced in both skeletal muscle and serum in CKD. Humanin in serum correlated positively to circulating TNF levels. Reduced MDP levels in skeletal muscle were associated with lower mitochondrial density and evidence of oxidative stress. These results indicate a differential regulation of MDPs in CKD and suggest an alternative site for humanin production than skeletal muscle in the uremic milieu. MDP levels were linked to systemic inflammation and evidence of oxidative stress in the muscle, two hallmark features of premature aging and uremia.

Original languageEnglish (US)
Pages (from-to)F1122-F1131
JournalAmerican journal of physiology. Renal physiology
Volume317
Issue number5
DOIs
StatePublished - Nov 1 2019

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Chronic Renal Insufficiency
Skeletal Muscle
Peptides
Mitochondria
Premature Aging
Muscles
Oxidative Stress
Serum
Uremia
humanin
Glomerular Filtration Rate
Open Reading Frames
Cell Survival
Apoptosis
Inflammation
Phenotype
Kidney
Glucose
Proteins

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Liu, Chang ; Gidlund, Eva Karin ; Witasp, Anna ; Qureshi, Abdul Rashid ; Söderberg, Magnus ; Thorell, Anders ; Nader, Gustavo A. ; Barany, Peter ; Stenvinkel, Peter ; von Walden, Ferdinand. / Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease. In: American journal of physiology. Renal physiology. 2019 ; Vol. 317, No. 5. pp. F1122-F1131.
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Liu, C, Gidlund, EK, Witasp, A, Qureshi, AR, Söderberg, M, Thorell, A, Nader, GA, Barany, P, Stenvinkel, P & von Walden, F 2019, 'Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease', American journal of physiology. Renal physiology, vol. 317, no. 5, pp. F1122-F1131. https://doi.org/10.1152/ajprenal.00202.2019

Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease. / Liu, Chang; Gidlund, Eva Karin; Witasp, Anna; Qureshi, Abdul Rashid; Söderberg, Magnus; Thorell, Anders; Nader, Gustavo A.; Barany, Peter; Stenvinkel, Peter; von Walden, Ferdinand.

In: American journal of physiology. Renal physiology, Vol. 317, No. 5, 01.11.2019, p. F1122-F1131.

Research output: Contribution to journalArticle

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T1 - Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease

AU - Liu, Chang

AU - Gidlund, Eva Karin

AU - Witasp, Anna

AU - Qureshi, Abdul Rashid

AU - Söderberg, Magnus

AU - Thorell, Anders

AU - Nader, Gustavo A.

AU - Barany, Peter

AU - Stenvinkel, Peter

AU - von Walden, Ferdinand

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Advanced chronic kidney disease (CKD) is characterized by a premature aging phenotype of multifactorial origin. Mitochondrial dysfunction is prevalent in CKD and has been proposed as a major contributor to poor muscle function. Although the mitochondria-derived peptides (MDPs) humanin and mitochondrial open reading frame of 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis, and glucose control, the implications of MDP in CKD are unknown. We investigated humanin and MOTS-c protein expression in skeletal muscle and serum levels in CKD at stage 5 (glomerular filtration rate: <15 ml/min) patients and age-matched controls with normal renal function. Whereas circulating levels of humanin were increased in CKD, local muscle expression was reduced. In contrast, MOTS-c levels were reduced in both skeletal muscle and serum in CKD. Humanin in serum correlated positively to circulating TNF levels. Reduced MDP levels in skeletal muscle were associated with lower mitochondrial density and evidence of oxidative stress. These results indicate a differential regulation of MDPs in CKD and suggest an alternative site for humanin production than skeletal muscle in the uremic milieu. MDP levels were linked to systemic inflammation and evidence of oxidative stress in the muscle, two hallmark features of premature aging and uremia.

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