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Myofibrillar protein and mRNA expression in Acute Quadriplegic Myopathy: A longitudinal study
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
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Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-94831OAI: oai:DiVA.org:uu-94831DiVA: diva2:168826
Available from: 2006-09-18 Created: 2006-09-18 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Cellular and Molecular Mechanisms Underlying Acute Quadriplegic Myopathy: Studies in Experimental Animal Models and Intensive Care Unit Patients
Open this publication in new window or tab >>Cellular and Molecular Mechanisms Underlying Acute Quadriplegic Myopathy: Studies in Experimental Animal Models and Intensive Care Unit Patients
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The combination of a severe systemic illness, corticosteroids, and neuromuscular blocking agents in patients on the mechanical ventilator often results in a condition known as Acute Quadriplegic Myopathy (AQM). While severe weakness of all spinal nerve innervated muscles is known to be a significant clinical characteristic of the disease, this symptom is typically not recognized until the disease has progressed to an advanced stage. End result effects have been classified, which include the loss of the thick filament, or myosin heavy chain, an in-excitable muscle membrane, and an up-regulation of protein degradation; however, there is little known about the acute stage of AQM. This project has focused on understanding the underlying mechanisms of AQM, specifically in regard to protein synthesis, both at the mRNA and nuclear transcription levels. To study the early stages of the disease two animal models have been developed: rat and pig. Further, we have examined AQM muscle tissue, to investigate the similarities of our animal models to patients, as well as to study the recovery process. Particular interest was directed on the myofibrillar proteins myosin (MyHC) and actin, as they are the primary proteins involved in muscle contraction, as well as the myosin associated proteins, myosin binding protein C and H.

At the mRNA level, MyHC and actin are both down-regulated in response to AQM. The myosin binding proteins are affected differently, with H protein increasing during severe atrophy and C protein either being slightly down-regulated or unchanged. Nuclear transcription factors were also affected, with such factors as MuRF1 and MAFbx up-regulated.

Thus far results have shown that protein synthesis is altered in AQM and largely contributes to both the development and recovery of the disease. The pathways of protein synthesis may prove to be an ideal target for the prevention of AQM and/or symptom alleviation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 79 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 171
Neurosciences, Acute Quadriplegic Myopathy, intensive care unit, atrophy, myosin heavy chain, actin, myosin binding proteins, nuclear transcription factors, mRNA, Neurovetenskap
urn:nbn:se:uu:diva-7133 (URN)91-554-6646-X (ISBN)
Public defence
2006-10-10, Enghoffsalen, University Hospital, Akademiska Sjukhuset, Ing 50, Uppsala, 09:00
Available from: 2006-09-18 Created: 2006-09-18Bibliographically approved

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