title: In vivo high-resolution magic angle spinning magnetic and electron paramagnetic resonance spectroscopic analysis of mitochondria-targeted peptide in Drosophila melanogaster with trauma-induced thoracic injury.
abstract: Trauma is the most common cause of mortality among individuals aged between 1 and 44 years and the third leading cause of mortality overall in the US. In this study, we examined the effects of trauma on the expression of genes in Drosophila melanogaster, a useful model for investigating genetics and physiology. After trauma was induced by a non-lethal needle puncture of the thorax, we observed the differential expression of genes encoding for mitochondrial uncoupling proteins, as well as those encoding for apoptosis-related and insulin signaling-related proteins, thus indicating muscle functional dysregulation. These results prompted us to examine the link between insulin signaling and mitochondrial dysfunction using in vivo nuclear magnetic resonance (NMR) with complementary electron paramagnetic resonance (EPR) spectroscopy. Trauma significantly increased insulin resistance biomarkers, and the NMR spectral profile of the aged flies with trauma-induced thoracic injury resembled that of insulin-resistant chico mutant flies. In addition, the mitochondrial redox status, as measured by EPR, was significantly altered following trauma, indicating mitochondrial uncoupling. A mitochondria-targeted compound, Szeto-Schiller (SS)-31 that promotes adenosine triphosphate (ATP) synthesis normalized the NMR spectral profile, as well as the mitochondrial redox status of the flies with trauma-induced thoracic injury, as assessed by EPR. Based on these findings, we propose a molecular mechanism responsible for trauma-related mortality and also propose that trauma sequelae in aging are linked to insulin signaling and mitochondrial dysfunction. Our findings further suggest that SS-31 attenuates trauma-associated pathological changes.
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Constantinou
authors.affiliation: Molecular Surgery Laboratory, Center for Surgery, Innovation and Bioengineering, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Yiorgos
authors.initials: Y
authors.lastname: Apidianakis
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Psychogios
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Righi
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Mindrinos
authors.affiliation: EPR Center for Viable Systems, Department of Diagnostic Radiology, The Geisel School of Medicine, Lebanon, NH, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Khan
authors.affiliation: EPR Center for Viable Systems, Department of Diagnostic Radiology, The Geisel School of Medicine, Lebanon, NH, USA.
authors.forename: Harold M
authors.initials: HM
authors.lastname: Swartz
authors.affiliation: Department of Pharmacology, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Hazel H
authors.initials: HH
authors.lastname: Szeto
authors.affiliation: Center for Surgery, Innovation and Bioengineering, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.affiliation: Molecular Surgery Laboratory, Center for Surgery, Innovation and Bioengineering, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Rahme
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: A Aria
authors.initials: AA
authors.lastname: Tzika
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D013898:Thoracic Injuries / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000071256:Uncoupling Protein 1; D014947:Wounds and Injuries / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D009842:Oligopeptides; D000071256:Uncoupling Protein 1; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D000255:Adenosine Triphosphate