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Impaired autophagy, chaperone expression, and protein synthesis in response to critical illness interventions in porcine skeletal muscle

Banduseela, Varuna (author)
Uppsala universitet,Klinisk neurofysiologi
Chen, Yi-wen (author)
Göransson Kultima, Hanna (author)
Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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Norman, Holly (author)
Uppsala universitet,Klinisk neurofysiologi,Department of Medicine, University of Wisconsin, Madison, Wisconsin
Aare, Sudhakar (author)
Uppsala universitet,Klinisk neurofysiologi
Radell, Peter (author)
Karolinska Institutet
Eriksson, Lars (author)
Karolinska Institutet
Hoffman, Eric (author)
Larsson, Lars (author)
Uppsala universitet,Klinisk neurofysiologi,Department of Biobehavioral Health, The Pennsylvania State University, University Park, Pennsylvania
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 (creator_code:org_t)
American Physiological Society, 2013
2013
English.
In: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 45:12, s. 477-486
Related links:
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Critical illness myopathy (CIM) is characterized by a preferential loss of the motor protein myosin, muscle wasting, and impaired muscle function in critically ill intensive care unit (ICU) patients. CIM is associated with severe morbidity and mortality and has a significant negative socioeconomic effect. Neuromuscular blocking agents, corticosteroids, sepsis, mechanical ventilation, and immobilization have been implicated as important risk factors, but the causal relationship between CIM and the risk factors has not been established. A porcine ICU model has been used to determine the immediate molecular and cellular cascades that may contribute to the pathogenesis prior to myosin loss and extensive muscle wasting. Expression profiles have been compared between pigs exposed to the ICU interventions, i.e., mechanically ventilated, sedated, and immobilized for 5 days, with pigs exposed to critical illness interventions, i.e., neuromuscular blocking agents, corticosteroids, and induced sepsis in addition to the ICU interventions for 5 days. Impaired autophagy as well as impaired chaperone expression and protein synthesis were observed in the skeletal muscle in response to critical illness interventions. A novel finding in this study is impaired core autophagy machinery in response to critical illness interventions, which when in concert with downregulated chaperone expression and protein synthesis may collectively affect the proteostasis in skeletal muscle and may exacerbate the disease progression in CIM.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

Keyword

intensive care unit; porcine ICU model; autophagy; chaperones; protein synthesis; skeletal muscle; critical illness myopathy and skeletal muscle proteostasis
Medical Cell Biology
Medicinsk cellbiologi

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