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Mechanisms Regulating Muscle Protein Synthesis in CKD
Liping Zhang1, Qin Chen2, Zihong Chen3
1Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas lipingz@bcm.edu.
Journal of the American Society of Nephrology : JASN
|August 9, 2020
Summary
Chronic kidney disease (CKD) causes muscle loss by suppressing protein synthesis via nucleolar protein 66 (NO66). Blocking NO66 in mice restored muscle mass and protein synthesis, suggesting new therapeutic targets.
Area of Science:
- Nephrology
- Molecular Biology
- Muscle Physiology
Background:
- Chronic kidney disease (CKD) is associated with muscle protein loss, partly due to suppressed muscle protein synthesis.
- Increased expression of nucleolar protein 66 (NO66) is observed in muscles of CKD models and patients, linked to inflammation and NF-κB signaling.
Purpose of the Study:
- To investigate the role of NO66 in CKD-induced muscle atrophy.
- To elucidate the molecular mechanisms by which NO66 affects muscle protein synthesis and mass in CKD.
Main Methods:
- A mouse model of CKD was established using subtotal nephrectomy.
- Muscle-specific NO66 knockout mice (MCK-NO66) were generated by crossing NO66flox/flox with MCK-Cre mice.
- The impact of NO66 deletion on muscle mass, protein synthesis, and epigenetic markers was assessed.
Main Results:
- Muscle-specific knockout of NO66 prevented CKD-induced muscle mass loss and enhanced protein synthesis in mice.
- NO66 suppresses ribosomal biogenesis through its demethylase activity, reducing H3K4me3 and H3K36me3 enrichment on ribosomal DNA.
- Deletion of NO66 led to increased ribosomal RNA, pre-ribosomal RNA, and overall protein synthesis in muscle cells and tissues.
Conclusions:
- CKD suppresses muscle protein synthesis via NO66-mediated epigenetic mechanisms.
- Targeting NO66 presents a potential therapeutic strategy to counteract muscle wasting in CKD patients.
Keywords:
chronic kidney diseaseepigeneticsmuscle wastingprotein metabolismprotein synthesisribosomal RNA transcriptionMore Related Videos
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