title: A Proteomic Approach to Identify Alterations in the Small Ubiquitin-like Modifier (SUMO) Network during Controlled Mechanical Ventilation in Rat Diaphragm Muscle.
abstract: 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 within vitroSUMOylation 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. Username: reviewer26663@ebi.ac.uk, Password: rwcP5W0o.
authors.affiliation: From the ‡Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SE-17177, Sweden.
authors.forename: Arvind Venkat
authors.initials: AV
authors.lastname: Namuduri
authors.affiliation: From the ‡Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SE-17177, Sweden.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Heras
authors.affiliation: §Department of Chemistry-BMC, Analytical Chemistry and Science for Lab Laboratory, Uppsala University, Box 599, Uppsala, SE-75124, Sweden.|¶Medicine and Pharmacy Research Center, Binzhou Medical University, Laishan District, No. 346, Guanhai Road, Yantai, Shandong Province, 264003 China.
authors.forename: Jia
authors.initials: J
authors.lastname: Mi
authors.affiliation: From the ‡Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SE-17177, Sweden.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cacciani
authors.affiliation: §Department of Chemistry-BMC, Analytical Chemistry and Science for Lab Laboratory, Uppsala University, Box 599, Uppsala, SE-75124, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Hörnaeus
authors.affiliation: §Department of Chemistry-BMC, Analytical Chemistry and Science for Lab Laboratory, Uppsala University, Box 599, Uppsala, SE-75124, Sweden.
authors.forename: Anne
authors.initials: A
authors.lastname: Konzer
authors.affiliation: §Department of Chemistry-BMC, Analytical Chemistry and Science for Lab Laboratory, Uppsala University, Box 599, Uppsala, SE-75124, Sweden.
authors.forename: Sara Bergström
authors.initials: SB
authors.lastname: Lind
authors.affiliation: From the ‡Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SE-17177, Sweden.|‖Department of Biobehavioral Health, The Pennsylvania State University, University Park, Pennsylvania 16801; and.|**Department of Clinical Neuroscience, Clinical Neurophysiology, Karolinska Institutet, Stockholm, SE-17177, Sweden.
authors.forename: Lars
authors.identifier: 0000-0002-6440-1458
authors.initials: L
authors.lastname: Larsson
authors.affiliation: From the ‡Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SE-17177, Sweden; stefano.gastaldello@ki.se.
authors.forename: Stefano
authors.identifier: 0000-0001-7369-8452
authors.initials: S
authors.lastname: Gastaldello
mesh_terms: D000818:Animals; D054810:Deep Sedation; D003964:Diaphragm / Q000378:metabolism*; D005260:Female; D019148:Neuromuscular Blockade; D040901:Proteomics; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins