A Proteomic Approach to Identify Alterations in the Small Ubiquitin-like Modifier (SUMO) Network during Controlled Mechanical Ventilation in Rat Diaphragm Muscle

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Namuduri, Arvind VenkatKarolinska Institutet (author)

A Proteomic Approach to Identify Alterations in the Small Ubiquitin-like Modifier (SUMO) Network during Controlled Mechanical Ventilation in Rat Diaphragm Muscle

Article/chapterEnglish2017

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AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC,2017
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LIBRIS-ID:oai:DiVA.org:uu-327143
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-327143URI
https://doi.org/10.1074/mcp.M116.066159DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:135947771URI

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Language:English
Summary in:English

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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.

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Heras, GabrielKarolinska Institutet (author)
Mi, JiaUppsala universitet,Analytisk kemi,Science for Life Laboratory, SciLifeLab,Binzhou Med Univ, Peoples R China.(Swepub:uu)jimix087 (author)
Cacciani, NicolaKarolinska Institutet (author)
Hörnaeus, KatarinaUppsala universitet,Science for Life Laboratory, SciLifeLab,Analytisk kemi(Swepub:uu)katho286 (author)
Konzer, AnneUppsala universitet,Analytisk kemi,Science for Life Laboratory, SciLifeLab(Swepub:uu)annko944 (author)
Bergström Lind, Sara,1977-Uppsala universitet,Analytisk kemi,Science for Life Laboratory, SciLifeLab(Swepub:uu)saber676 (author)
Larsson, LarsKarolinska Institutet (author)
Gastaldello, StefanoKarolinska Institutet (author)
Karolinska InstitutetAnalytisk kemi (creator_code:org_t)

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In:Molecular & Cellular Proteomics: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC16:6, s. 1081-10971535-94761535-9484

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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