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A Proteomic Approach to Identify Alterations in the Small Ubiquitin-like Modifier (SUMO) Network during Controlled Mechanical Ventilation in Rat Diaphragm Muscle
Karolinska Inst.
Karolinska Inst.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Binzhou Med Univ, Peoples R China..
Karolinska Inst.
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2017 (Engelska)Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 16, nr 6, s. 1081-1097Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The small ubiquitin-like modifier (SUMO) is as a regulator of many cellular functions by reversible conjugation to a broad number of substrates. Under endogenous or exogenous perturbations, the SUMO network becomes a fine sensor of stress conditions by alterations in the expression level of SUMO enzymes and consequently changing the status of SUMOylated proteins. The diaphragm is the major inspiratory muscle, which is continuously active under physiological conditions, but its structure and function is severely affected when passively displaced for long extents during mechanical ventilation (MV). An iatrogenic condition called Ventilator-Induced Diaphragm Dysfunction (VIDD) is a major cause of failure to wean patients from ventilator support but the molecular mechanisms underlying this dysfunction are not fully understood. Using a unique experimental Intensive Care Unit (ICU) rat model allowing long-term MV, diaphragm muscles were collected in rats control and exposed to controlled MV (CMV) for durations varying between 1 and 10 days. Endogenous SUMOylated diaphragm proteins were identified by mass spectrometry and validated with in vitro SUMOylation systems. Contractile, calcium regulator and mitochondrial proteins were of specific interest due to their putative involvement in VIDD. Differences were observed in the abundance of SUMOylated proteins between glycolytic and oxidative muscle fibers in control animals and high levels of SUMOylated proteins were present in all fibers during CMV. Finally, previously reported VIDD biomarkers and therapeutic targets were also identified in our datasets which may play an important role in response to muscle weakness seen in ICU patients. Data are available via ProteomeXchange with identifier PXD006085.

Ort, förlag, år, upplaga, sidor
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC , 2017. Vol. 16, nr 6, s. 1081-1097
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-327143DOI: 10.1074/mcp.M116.066159ISI: 000402576600009PubMedID: 28373296OAI: oai:DiVA.org:uu-327143DiVA, id: diva2:1136541
Forskningsfinansiär
Vetenskapsrådet, 8651Åke Wibergs Stiftelse, M14-0127Carl Tryggers stiftelse för vetenskaplig forskning , CST 15:57Magnus Bergvalls Stiftelse, 2015-01200Stiftelsen för internationalisering av högre utbildning och forskning (STINT)Stockholms läns landstingTillgänglig från: 2017-08-28 Skapad: 2017-08-28 Senast uppdaterad: 2018-01-13Bibliografiskt granskad

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Mi, JiaHörnaeus, KatarinaKonzer, AnneBergström Lind, Sara

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Mi, JiaHörnaeus, KatarinaKonzer, AnneBergström Lind, Sara
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