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Chaperone co-induce...
Chaperone co-inducer BGP-15 mitigates early contractile dysfunction of the soleus muscle in a rat ICU model
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- Cacciani, Nicola (författare)
- Karolinska Institutet
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- Salah, Heba (författare)
- Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Li, Meishan (författare)
- Karolinska Institutet
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- Akkad, Hazem (författare)
- Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Backeus, Anders (författare)
- Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Hedstrom, Yvette (författare)
- Karolinska Institutet
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- Jena, Bhanu P. (författare)
- Wayne State Univ, Sch Med, Dept Physiol, Detroit, MI 48201 USA.
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- Bergquist, Jonas (författare)
- Uppsala universitet,Analytisk kemi
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- Larsson, Lars (författare)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden (creator_code:org_t)
- 2019-12-18
- 2020
- Engelska.
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 229:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Aim Critical illness myopathy (CIM) represents a common consequence of modern intensive care, negatively impacting patient health and significantly increasing health care costs; however, there is no treatment available apart from symptomatic and supportive interventions. The chaperone co-inducer BGP-15 has previously been shown to have a positive effect on the diaphragm in rats exposed to the intensive care unit (ICU) condition. In this study, we aim to explore the effects of BGP-15 on a limb muscle (soleus muscle) in response to the ICU condition. Methods Sprague-Dawley rats were subjected to the ICU condition for 5, 8 and 10 days and compared with untreated sham-operated controls. Results BGP-15 significantly improved soleus muscle fibre force after 5 days exposure to the ICU condition. This improvement was associated with the protection of myosin from post-translational myosin modifications, improved mitochondrial structure/biogenesis and reduced the expression of MuRF1 and Fbxo31 E3 ligases. At longer durations (8 and 10 days), BGP-15 had no protective effect when the hallmark of CIM had become manifest, that is, preferential loss of myosin. Unrelated to the effects on skeletal muscle, BGP-15 had a strong positive effect on survival compared with untreated animals. Conclusions BGP-15 treatment improved soleus muscle fibre and motor protein function after 5 days exposure to the ICU condition, but not at longer durations (8 and 10 days) when the preferential loss of myosin was manifest. Thus, long-term CIM interventions targeting limb muscle fibre/myosin force generation capacity need to consider both the post-translational modifications and the loss of myosin.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- immobilization
- mechanical ventilation
- myopathy
- myosin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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