Weak by the machines: muscle motor protein dysfunction - a side effect of intensive care unit treatment.
Friedrich O, Diermeier S, Larsson L (2018)
Publication Language: English
Publication Status: Published
Publication Type: Journal article, Review article
Publication year: 2018
Journal
Book Volume: 222
Article Number: e12885
Journal Issue: 1
DOI: 10.1111/apha.12885
Abstract
Intensive care interventions involve periods of mechanical ventilation, sedation and complete mechanical silencing of patients. Critical illness myopathy (CIM) is an ICU-acquired myopathy that is associated with limb muscle weakness, muscle atrophy, electrical silencing of muscle and motor proteinopathy. The hallmark of CIM is a preferential muscle myosin loss due to increased catabolic and reduced anabolic activity. The ubiquitin proteasome pathway plays an important role, apart from recently identified novel mechanisms affecting non-lysosomal protein degradation or autophagy. CIM is not reproduced by pure disuse atrophy, denervation atrophy, steroid-induced atrophy or septic myopathy, although combinations of high-dose steroids and denervation can mimic CIM. New animal models of critical illness and ICU treatment (i.e. mechanical ventilation and complete immobilization) provide novel insights regarding the time course of protein synthesis and degradation alterations, and the role of protective chaperone activities in the process of myosin loss. Altered mechano-signalling seems involved in triggering a major part of myosin loss in experimental CIM models, and passive loading of muscle potently ameliorates the CIM phenotype. We provide a systematic overview of similarities and distinct differences in the signalling pathways involved in triggering muscle atrophy in CIM and isolated trigger factors. As preferential myosin loss is mostly determined from biochemistry analyses providing no spatial resolution of myosin loss processes within myofibres, we also provide first results monitoring myosin signal intensities during experimental ICU intervention using multi-photon Second Harmonic Generation microscopy. Our results confirm that myosin loss is an evenly distributed process within myofibres rather than being confined to hot spots.
Authors with CRIS profile
Oliver Friedrich
Lehrstuhl für Medizinische Biotechnologie (MBT)
Stefanie Nübler
Lehrstuhl für Medizinische Biotechnologie (MBT)
Related research project(s)
Progressive Muscle Dysfunction resulting from chronic Remodeling of Cellular Architecture in inherited Muscle Diseases
Advanced Second Harmonic Generation -
Microscopy and quantitative Morphometry in skeletal Muscles from Animal Models of Duchenne Muscular Dystrophy and Desminopathy
Nov. 1, 2013 - Aug. 30, 2018
Advanced Optical Laser Technologies for Life Sciences and personalized Medicine (ADVENDO-LIFE) (ADVENDO-LIFE)
Jan. 1, 2014 - Dec. 31, 2015
Involved external institutions
Sweden (SE)How to cite
APA:
Friedrich, O., Diermeier, S., & Larsson, L. (2018). Weak by the machines: muscle motor protein dysfunction - a side effect of intensive care unit treatment. Acta Physiologica, 222(1). https://doi.org/10.1111/apha.12885
MLA:
Friedrich, Oliver, Stefanie Diermeier, and Lars Larsson. "Weak by the machines: muscle motor protein dysfunction - a side effect of intensive care unit treatment." Acta Physiologica 222.1 (2018).
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