Summary of project PR000460

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000460. The data can be accessed directly via it's Project DOI: 10.21228/M8M027 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR000460
Project DOI:doi: 10.21228/M8M027
Project Title:The dystrophic muscle metabolome: effects of exercise and NO donor therapy
Project Summary:"In Duchenne and Becker muscular dystrophy (DMD, BMD), loss of the cytoskeletal protein dystrophin weakens the sarcolemma and disrupts cellular signaling, rendering the diseased muscles susceptible to contractioninduced damage. We and others have shown that loss of neuronal nitric oxide synthase (nNOSμ) from the sarcolemma of dystrophin-deficient muscle causes functional muscle ischemia during exercise due to unopposed sympathetic vasoconstriction, thereby exacerbating fatigue and injury of the diseased muscles. Genetic and pharmacologic strategies targeting nNOSμ-NO signaling ameliorate functional muscle ischemia, as well as many other features of the dystrophic phenotype in the mdx mouse model of DMD/BMD. These findings suggest that the therapeutic benefit of NO likely extends beyond its vascular effects. A growing body of evidence indicates that NO directly influences muscle metabolism through effects on glucose transport as well as mitochondrial biogenesis and function. Both nNOS-/- mice and mdx mice exhibit muscle mitochondrial dysfunction, decreased resistance to fatigue, and exercise-induced muscle injury, suggesting a causal role of nNOSμ-NO deficiency. However, the specific metabolic changes resulting from reduced NO signaling that might render dystrophic muscle susceptible to fatigue and use-dependent injury remain poorly defined. Therefore, the goal of this pilot metabolomics study is to identify the unique biochemical profiles of skeletal and cardiac muscles of mdx mice to gain further mechanistic insight into the pathophysiological role of NO deficiency in muscular dystrophy. In Aim 1, we will characterize the skeletal and cardiac muscle metabolomes of mdx and nNOS-/- mice at rest and following a single bout of treadmill exercise with the goal of discovering common metabolic signatures caused by loss of NO signaling. In Aim 2, we will evaluate the potential of a NO donor drug that is under development as a therapeutic for DMD/BMD to improve the skeletal and cardiac muscle metabolomes in mdx mice. As a result of this pilot study, we hope to gain new understanding of the metabolic derangements in dystrophin-deficient muscle, insight into the therapeutic effects of NO replacement, and to identify new pathogenic mechanisms and putative therapeutic targets that will form the basis of future grant applications."
Institute:Mayo Clinic
Last Name:Thomas
First Name:Gail
Address:Penn State Hershey Heart and Vascular Institute Penn State College of Medicine 500 University Drive, MC H047 Hershey, PA 17033
Email:gthomas4@hmc.psu.edu
Phone:717-531-0003, ext. 287087

Summary of all studies in project PR000460

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST000645 Effects of Exercise on Dystrophic Mouse Muscle Amino Acids (part I) Mus musculus Mayo Clinic MS 2019-07-17 1 30 Not available
ST000646 Effects of Exercise on Dystrophic Mouse Muscle TCA Cycle (part II) Mus musculus Mayo Clinic MS 2019-07-17 1 30 Not available
ST000647 Effects of Exercise on Dystrophic Mouse Muscle Non-Esterified Fatty Acids (part III) Mus musculus Mayo Clinic MS 2019-07-17 1 30 Not available
ST000648 Effects of NO Donor Therapy on the Dystrophic Mouse Muscle Amino Acids (part IV) Mus musculus Mayo Clinic MS 2019-07-17 1 30 Not available
ST000649 Effects of NO Donor Therapy on the Dystrophic Mouse Muscle Non-Esterified Fatty Acids (part V) Mus musculus Mayo Clinic MS 2019-07-17 1 30 Not available
ST000650 Effects of NO Donor Therapy on the Dystrophic Mouse Muscle TCA Cycle (part VI) Mus musculus Mayo Clinic MS 2019-07-17 1 30 Not available
ST000651 Effects of NO Donor Therapy on the Dystrophic Mouse Heart Metabolome (part VII) Mus musculus Mayo Clinic MS* 2019-07-17 1 240 Uploaded data (3.2M)
ST000652 Effects of NO Donor Therapy on the Dystrophic Mouse Quadricep Metabolome (part VIII) Mus musculus Mayo Clinic MS* 2019-07-17 1 240 Uploaded data (1.7M)
ST000653 Effects of Exercise on Dystrophic Mouse Heart Meabolome (part IX) Mus musculus Mayo Clinic MS* 2019-07-17 1 240 Uploaded data (1.6M)
ST000654 Effects of Exercise on Dystrophic Mouse Quadricep Meabolome (part X) Mus musculus Mayo Clinic MS* 2019-07-17 1 226 Uploaded data (1.8M)
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