Åpne denne publikasjonen i ny fane eller vindu >>Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
Univ Padua, Dept Womens & Childrens Hlth, Clin Genet Unit, I-35128 Padua, Italy..
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6726 Szeged, Hungary..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden.;Penn State Univ, Dept Neurosci, Hershey, PA 17033 USA..
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84112 USA.;Binzhou Med Univ, Precis Med, Yantai 264003, Shandong, Peoples R China..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6726 Szeged, Hungary..
Univ Padua, Dept Womens & Childrens Hlth, Clin Genet Unit, I-35128 Padua, Italy..
Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden.;Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA.;Karolinska Inst, Clin Neurophysiol, Dept Clin Neurosci, SE-17777 Stockholm, Sweden..
Vise andre…
2016 (engelsk)Inngår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 8, nr 350, artikkel-id 350ra103Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]
Ventilation-induced diaphragm dysfunction (VIDD) is a marked decline in diaphragm function in response to mechanical ventilation, which has negative consequences for individual patients' quality of life and for the health care system, but specific treatment strategies are still lacking. We used an experimental intensive care unit (ICU) model, allowing time-resolved studies of diaphragm structure and function in response to long-term mechanical ventilation and the effects of a pharmacological intervention (the chaperone co-inducer BGP-15). The marked loss of diaphragm muscle fiber function in response to mechanical ventilation was caused by post-translational modifications (PTMs) of myosin. In a rat model, 10 days of BGP-15 treatment greatly improved diaphragm muscle fiber function (by about 100%), although it did not reverse diaphragm atrophy. The treatment also provided protection from myosin PTMs associated with HSP72 induction and PARP-1 inhibition, resulting in improvement of mitochondrial function and content. Thus, BGP-15 may offer an intervention strategy for reducing VIDD in mechanically ventilated ICU patients.
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-303060 (URN)10.1126/scitranslmed.aaf7099 (DOI)000380780000005 ()
Eksternt samarbeid:
Forskningsfinansiär
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Swedish Research Council, 8651; 4423; 4870; 3074EU, European Research Council, CT-223756; COST CM1001The Karolinska Institutet's Research FoundationStockholm County CouncilNovo Nordisk, 100193
2016-09-142016-09-142018-01-10bibliografisk kontrollert