#METABOLOMICS WORKBENCH hormel101_20170623_152317 DATATRACK_ID:1101 STUDY_ID:ST000652 ANALYSIS_ID:AN000990 PROJECT_ID:PR000460 VERSION 1 CREATED_ON June 26, 2017, 8:34 am #PROJECT PR:PROJECT_TITLE The dystrophic muscle metabolome: effects of exercise and NO donor therapy PR:PROJECT_SUMMARY "In Duchenne and Becker muscular dystrophy (DMD, BMD), loss of the cytoskeletal PR:PROJECT_SUMMARY protein dystrophin weakens the sarcolemma and disrupts cellular signaling, PR:PROJECT_SUMMARY rendering the diseased muscles susceptible to contractioninduced damage. We and PR:PROJECT_SUMMARY others have shown that loss of neuronal nitric oxide synthase (nNOSμ) from the PR:PROJECT_SUMMARY sarcolemma of dystrophin-deficient muscle causes functional muscle ischemia PR:PROJECT_SUMMARY during exercise due to unopposed sympathetic vasoconstriction, thereby PR:PROJECT_SUMMARY exacerbating fatigue and injury of the diseased muscles. Genetic and PR:PROJECT_SUMMARY pharmacologic strategies targeting nNOSμ-NO signaling ameliorate functional PR:PROJECT_SUMMARY muscle ischemia, as well as many other features of the dystrophic phenotype in PR:PROJECT_SUMMARY the mdx mouse model of DMD/BMD. These findings suggest that the therapeutic PR:PROJECT_SUMMARY benefit of NO likely extends beyond its vascular effects. A growing body of PR:PROJECT_SUMMARY evidence indicates that NO directly influences muscle metabolism through effects PR:PROJECT_SUMMARY on glucose transport as well as mitochondrial biogenesis and function. Both PR:PROJECT_SUMMARY nNOS-/- mice and mdx mice exhibit muscle mitochondrial dysfunction, decreased PR:PROJECT_SUMMARY resistance to fatigue, and exercise-induced muscle injury, suggesting a causal PR:PROJECT_SUMMARY role of nNOSμ-NO deficiency. However, the specific metabolic changes resulting PR:PROJECT_SUMMARY from reduced NO signaling that might render dystrophic muscle susceptible to PR:PROJECT_SUMMARY fatigue and use-dependent injury remain poorly defined. Therefore, the goal of PR:PROJECT_SUMMARY this pilot metabolomics study is to identify the unique biochemical profiles of PR:PROJECT_SUMMARY skeletal and cardiac muscles of mdx mice to gain further mechanistic insight PR:PROJECT_SUMMARY into the pathophysiological role of NO deficiency in muscular dystrophy. In Aim PR:PROJECT_SUMMARY 1, we will characterize the skeletal and cardiac muscle metabolomes of mdx and PR:PROJECT_SUMMARY nNOS-/- mice at rest and following a single bout of treadmill exercise with the PR:PROJECT_SUMMARY goal of discovering common metabolic signatures caused by loss of NO signaling. PR:PROJECT_SUMMARY In Aim 2, we will evaluate the potential of a NO donor drug that is under PR:PROJECT_SUMMARY development as a therapeutic for DMD/BMD to improve the skeletal and cardiac PR:PROJECT_SUMMARY muscle metabolomes in mdx mice. As a result of this pilot study, we hope to gain PR:PROJECT_SUMMARY new understanding of the metabolic derangements in dystrophin-deficient muscle, PR:PROJECT_SUMMARY insight into the therapeutic effects of NO replacement, and to identify new PR:PROJECT_SUMMARY pathogenic mechanisms and putative therapeutic targets that will form the basis PR:PROJECT_SUMMARY of future grant applications." PR:INSTITUTE Mayo Clinic PR:LAST_NAME Thomas PR:FIRST_NAME Gail PR:ADDRESS Penn State Hershey Heart and Vascular Institute Penn State College of Medicine PR:ADDRESS 500 University Drive, MC H047 Hershey, PA 17033 PR:EMAIL gthomas4@hmc.psu.edu PR:PHONE 717-531-0003, ext. 287087 #STUDY ST:STUDY_TITLE Effects of NO Donor Therapy on the Dystrophic Mouse Quadricep Metabolome (part ST:STUDY_TITLE VIII) ST:STUDY_SUMMARY For this aim, we will only use male mdx mice. We will study three groups treated ST:STUDY_SUMMARY for 7 days with vehicle, naproxcinod (i.e., NO-naproxen), or naproxen (n = 10 ST:STUDY_SUMMARY each group). Two hours after the final treatment, half the mice in each group ST:STUDY_SUMMARY will be run to exhaustion on a treadmill. The heart and gastrocnemius, soleus, ST:STUDY_SUMMARY and quadriceps muscles of one hindlimb will be sent to the Mayo Clinic ST:STUDY_SUMMARY Metabolomics Resource Core. The heart and quadriceps muscle will be used for ST:STUDY_SUMMARY untargeted metabolomics profiling (LC/MS). ST:INSTITUTE Mayo Clinic ST:LAST_NAME Thomas ST:FIRST_NAME Gail ST:ADDRESS Penn State Hershey Heart and Vascular Institute Penn State College of Medicine ST:ADDRESS 500 University Drive, MC H047 Hershey, PA 17033 ST:EMAIL gthomas4@hmc.psu.edu ST:PHONE 717-531-0003, ext. 287087 #SUBJECT SU:SUBJECT_TYPE Mouse SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS ms5861-1 nC18-20may16-001-r001_2 Group:SED-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-1 nC18-20may16-001-r002_2 Group:SED-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-2 nC18-20may16-002-r001_2 Group:RUN-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-2 nC18-20may16-002-r002_2 Group:RUN-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-3 nC18-20may16-003-r001_2 Group:RUN-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-3 nC18-20may16-003-r002_2 Group:RUN-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-4 nC18-20may16-004-r001_2 Group:RUN-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-4 nC18-20may16-004-r002_2 Group:RUN-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-5 nC18-20may16-005-r001_2 Group:SED-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-5 nC18-20may16-005-r002_2 Group:SED-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-6 nC18-20may16-006-r001_2 Group:RUN-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-6 nC18-20may16-006-r002_2 Group:RUN-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-7 nC18-20may16-007-r001_2 Group:SED-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-7 nC18-20may16-007-r002_2 Group:SED-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-8 nC18-20may16-008-r001_2 Group:RUN-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-8 nC18-20may16-008-r002_2 Group:RUN-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-9 nC18-20may16-009-r001_2 Group:SED-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-9 nC18-20may16-009-r002_2 Group:SED-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-10 nC18-20may16-010-r001_2 Group:SED-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-10 nC18-20may16-010-r002_2 Group:SED-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-11 nC18-20may16-011-r001_2 Group:RUN-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-11 nC18-20may16-011-r002_2 Group:RUN-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-12 nC18-20may16-012-r001_2 Group:RUN-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-12 nC18-20may16-012-r002_2 Group:RUN-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-13 nC18-20may16-013-r001_2 Group:RUN-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-13 nC18-20may16-013-r002_2 Group:RUN-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-14 nC18-20may16-014-r001_2 Group:SED-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-14 nC18-20may16-014-r002_2 Group:SED-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-15 nC18-20may16-015-r001_2 Group:SED-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-15 nC18-20may16-015-r002_2 Group:SED-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-16 nC18-20may16-016-r001_2 Group:RUN-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-16 nC18-20may16-016-r002_2 Group:RUN-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-17 nC18-20may16-017-r001_2 Group:SED-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-17 nC18-20may16-017-r002_2 Group:SED-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-18 nC18-20may16-018-r001_2 Group:RUN-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-18 nC18-20may16-018-r002_2 Group:RUN-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-19 nC18-20may16-019-r001_2 Group:RUN-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-19 nC18-20may16-019-r002_2 Group:RUN-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-20 nC18-20may16-020-r001_2 Group:RUN-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-20 nC18-20may16-020-r002_2 Group:RUN-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-21 nC18-20may16-021-r001_2 Group:SED-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-21 nC18-20may16-021-r002_2 Group:SED-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-22 nC18-20may16-022-r001_2 Group:RUN-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-22 nC18-20may16-022-r002_2 Group:RUN-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-23 nC18-20may16-023-r001_2 Group:RUN-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-23 nC18-20may16-023-r002_2 Group:RUN-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-24 nC18-20may16-024-r001_2 Group:RUN-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-24 nC18-20may16-024-r002_2 Group:RUN-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-25 nC18-20may16-025-r001_2 Group:SED-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-25 nC18-20may16-025-r002_2 Group:SED-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-26 nC18-20may16-026-r001_2 Group:SED-Naproxcinod | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-26 nC18-20may16-026-r002_2 Group:SED-Naproxcinod | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-27 nC18-20may16-027-r001_2 Group:SED-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-27 nC18-20may16-027-r002_2 Group:SED-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-28 nC18-20may16-028-r001_2 Group:SED-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-28 nC18-20may16-028-r002_2 Group:SED-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-29 nC18-20may16-029-r001_2 Group:SED-Vehicle | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-29 nC18-20may16-029-r002_2 Group:SED-Vehicle | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-30 nC18-20may16-030-r001_2 Group:SED-Naproxen | rep:1 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-30 nC18-20may16-030-r002_2 Group:SED-Naproxen | rep:2 chromatography=NC18 SUBJECT_SAMPLE_FACTORS ms5861-1 pC18-4may16-001-r001_1 Group:SED-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-1 pC18-4may16-001-r002_1 Group:SED-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-2 pC18-4may16-002-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-2 pC18-4may16-002-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-3 pC18-4may16-003-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-3 pC18-4may16-003-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-4 pC18-4may16-004-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-4 pC18-4may16-004-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-5 pC18-4may16-005-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-5 pC18-4may16-005-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-6 pC18-4may16-006-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-6 pC18-4may16-006-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-7 pC18-4may16-007-r001_1 Group:SED-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-7 pC18-4may16-007-r002_1 Group:SED-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-8 pC18-4may16-008-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-8 pC18-4may16-008-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-9 pC18-4may16-009-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-9 pC18-4may16-009-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-10 pC18-4may16-010-r001_1 Group:SED-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-10 pC18-4may16-010-r002_1 Group:SED-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-11 pC18-4may16-011-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-11 pC18-4may16-011-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-12 pC18-4may16-012-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-12 pC18-4may16-012-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-13 pC18-4may16-013-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-13 pC18-4may16-013-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-14 pC18-4may16-014-r001_1 Group:SED-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-14 pC18-4may16-014-r002_1 Group:SED-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-15 pC18-4may16-015-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-15 pC18-4may16-015-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-16 pC18-4may16-016-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-16 pC18-4may16-016-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-17 pC18-4may16-017-r001_1 Group:SED-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-17 pC18-4may16-017-r002_1 Group:SED-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-18 pC18-4may16-018-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-18 pC18-4may16-018-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-19 pC18-4may16-019-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-19 pC18-4may16-019-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-20 pC18-4may16-020-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-20 pC18-4may16-020-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-21 pC18-4may16-021-r001_1 Group:SED-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-21 pC18-4may16-021-r002_1 Group:SED-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-22 pC18-4may16-022-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-22 pC18-4may16-022-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-23 pC18-4may16-023-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-23 pC18-4may16-023-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-24 pC18-4may16-024-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-24 pC18-4may16-024-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-25 pC18-4may16-025-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-25 pC18-4may16-025-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-26 pC18-4may16-026-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-26 pC18-4may16-026-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-27 pC18-4may16-027-r001_1 Group:SED-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-27 pC18-4may16-027-r002_1 Group:SED-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-28 pC18-4may16-028-r001_1 Group:SED-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-28 pC18-4may16-028-r002_1 Group:SED-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-29 pC18-4may16-029-r001_1 Group:SED-Vehicle | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-29 pC18-4may16-029-r002_1 Group:SED-Vehicle | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-30 pC18-4may16-030-r001_1 Group:SED-Naproxen | rep:1 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-30 pC18-4may16-030-r002_1 Group:SED-Naproxen | rep:2 chromatography=PC18 SUBJECT_SAMPLE_FACTORS ms5861-1 nhilic-6may16-001-r001 Group:SED-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-1 nhilic-6may16-001-r002 Group:SED-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-2 nhilic-6may16-002-r001 Group:RUN-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-2 nhilic-6may16-002-r002 Group:RUN-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-3 nhilic-6may16-003-r001 Group:RUN-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-3 nhilic-6may16-003-r002 Group:RUN-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-4 nhilic-6may16-004-r001 Group:RUN-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-4 nhilic-6may16-004-r002 Group:RUN-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-5 nhilic-6may16-005-r001 Group:SED-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-5 nhilic-6may16-005-r002 Group:SED-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-6 nhilic-6may16-006-r001 Group:RUN-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-6 nhilic-6may16-006-r002 Group:RUN-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-7 nhilic-6may16-007-r001 Group:SED-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-7 nhilic-6may16-007-r002 Group:SED-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-8 nhilic-6may16-008-r001 Group:RUN-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-8 nhilic-6may16-008-r002 Group:RUN-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-9 nhilic-6may16-009-r001 Group:SED-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-9 nhilic-6may16-009-r002 Group:SED-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-10 nhilic-6may16-010-r001 Group:SED-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-10 nhilic-6may16-010-r002 Group:SED-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-11 nhilic-6may16-011-r001 Group:RUN-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-11 nhilic-6may16-011-r002 Group:RUN-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-12 nhilic-6may16-012-r001 Group:RUN-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-12 nhilic-6may16-012-r002 Group:RUN-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-13 nhilic-6may16-013-r001 Group:RUN-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-13 nhilic-6may16-013-r002 Group:RUN-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-14 nhilic-6may16-014-r001 Group:SED-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-14 nhilic-6may16-014-r002 Group:SED-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-15 nhilic-6may16-015-r001 Group:SED-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-15 nhilic-6may16-015-r002 Group:SED-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-16 nhilic-6may16-016-r001 Group:RUN-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-16 nhilic-6may16-016-r002 Group:RUN-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-17 nhilic-6may16-017-r001 Group:SED-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-17 nhilic-6may16-017-r002 Group:SED-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-18 nhilic-6may16-018-r001 Group:RUN-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-18 nhilic-6may16-018-r002 Group:RUN-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-19 nhilic-6may16-019-r001 Group:RUN-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-19 nhilic-6may16-019-r002 Group:RUN-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-20 nhilic-6may16-020-r001 Group:RUN-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-20 nhilic-6may16-020-r002 Group:RUN-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-21 nhilic-6may16-021-r001 Group:SED-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-21 nhilic-6may16-021-r002 Group:SED-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-22 nhilic-6may16-022-r001 Group:RUN-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-22 nhilic-6may16-022-r002 Group:RUN-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-23 nhilic-6may16-023-r001 Group:RUN-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-23 nhilic-6may16-023-r002 Group:RUN-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-24 nhilic-6may16-024-r001 Group:RUN-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-24 nhilic-6may16-024-r002 Group:RUN-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-25 nhilic-6may16-025-r001 Group:SED-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-25 nhilic-6may16-025-r002 Group:SED-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-26 nhilic-6may16-026-r001 Group:SED-Naproxcinod | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-26 nhilic-6may16-026-r002 Group:SED-Naproxcinod | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-27 nhilic-6may16-027-r001 Group:SED-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-27 nhilic-6may16-027-r002 Group:SED-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-28 nhilic-6may16-028-r001 Group:SED-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-28 nhilic-6may16-028-r002 Group:SED-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-29 nhilic-6may16-029-r001 Group:SED-Vehicle | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-29 nhilic-6may16-029-r002 Group:SED-Vehicle | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-30 nhilic-6may16-030-r001 Group:SED-Naproxen | rep:1 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-30 nhilic-6may16-030-r002 Group:SED-Naproxen | rep:2 chromatography=NHILIC SUBJECT_SAMPLE_FACTORS ms5861-1 philic-4may16-001-r001_1 Group:SED-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-1 philic-4may16-001-r002_1 Group:SED-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-2 philic-4may16-002-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-2 philic-4may16-002-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-3 philic-4may16-003-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-3 philic-4may16-003-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-4 philic-4may16-004-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-4 philic-4may16-004-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-5 philic-4may16-005-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-5 philic-4may16-005-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-6 philic-4may16-006-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-6 philic-4may16-006-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-7 philic-4may16-007-r001_1 Group:SED-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-7 philic-4may16-007-r002_1 Group:SED-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-8 philic-4may16-008-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-8 philic-4may16-008-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-9 philic-4may16-009-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-9 philic-4may16-009-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-10 philic-4may16-010-r001_1 Group:SED-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-10 philic-4may16-010-r002_1 Group:SED-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-11 philic-4may16-011-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-11 philic-4may16-011-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-12 philic-4may16-012-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-12 philic-4may16-012-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-13 philic-4may16-013-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-13 philic-4may16-013-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-14 philic-4may16-014-r001_1 Group:SED-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-14 philic-4may16-014-r002_1 Group:SED-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-15 philic-4may16-015-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-15 philic-4may16-015-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-16 philic-4may16-016-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-16 philic-4may16-016-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-17 philic-4may16-017-r001_1 Group:SED-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-17 philic-4may16-017-r002_1 Group:SED-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-18 philic-4may16-018-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-18 philic-4may16-018-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-19 philic-4may16-019-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-19 philic-4may16-019-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-20 philic-4may16-020-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-20 philic-4may16-020-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-21 philic-4may16-021-r001_1 Group:SED-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-21 philic-4may16-021-r002_1 Group:SED-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-22 philic-4may16-022-r001_1 Group:RUN-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-22 philic-4may16-022-r002_1 Group:RUN-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-23 philic-4may16-023-r001_1 Group:RUN-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-23 philic-4may16-023-r002_1 Group:RUN-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-24 philic-4may16-024-r001_1 Group:RUN-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-24 philic-4may16-024-r002_1 Group:RUN-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-25 philic-4may16-025-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-25 philic-4may16-025-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-26 philic-4may16-026-r001_1 Group:SED-Naproxcinod | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-26 philic-4may16-026-r002_1 Group:SED-Naproxcinod | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-27 philic-4may16-027-r001_1 Group:SED-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-27 philic-4may16-027-r002_1 Group:SED-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-28 philic-4may16-028-r001_1 Group:SED-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-28 philic-4may16-028-r002_1 Group:SED-Naproxen | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-29 philic-4may16-029-r001_1 Group:SED-Vehicle | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-29 philic-4may16-029-r002_1 Group:SED-Vehicle | rep:2 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-30 philic-4may16-030-r001_1 Group:SED-Naproxen | rep:1 chromatography=PHILIC SUBJECT_SAMPLE_FACTORS ms5861-30 philic-4may16-030-r002_1 Group:SED-Naproxen | rep:2 chromatography=PHILIC #COLLECTION CO:COLLECTION_SUMMARY Blood and Tissue Harvesting: Mice will be euthanized and blood will be taken by CO:COLLECTION_SUMMARY cardiac puncture, centrifuged, and the plasma will be stored at -80ºC. The CO:COLLECTION_SUMMARY heart, diaphragm, and muscles of both hindlimbs (gastrocnemius, soleus, CO:COLLECTION_SUMMARY quadriceps) will be dissected and snap frozen in liquid nitrogen. Tibialis CO:COLLECTION_SUMMARY anterior and plantaris muscles from both hindlimbs also will be dissected and CO:COLLECTION_SUMMARY one set will be snap frozen in liquid nitrogen while the other set will be CO:COLLECTION_SUMMARY mounted in OCT and frozen in isopentane cooled by liquid nitrogen. Cryosections CO:COLLECTION_SUMMARY will be used to evaluate disease activity and exercise-induced muscle injury by CO:COLLECTION_SUMMARY staining with: (a) hematoxylin and eosin to assess gross morphology, cellular CO:COLLECTION_SUMMARY infiltration, and necrosis, (b) anti-F4/80 to label macrophages, and (c) CO:COLLECTION_SUMMARY anti-IgG or IgM to label damaged muscle fibers. #TREATMENT TR:TREATMENT_SUMMARY "Studies will be performed in 12-16 week old male mdx mice, C57BL10 control TR:TREATMENT_SUMMARY mice, and nNOS-/- mice obtained from Jackson Laboratory. All protocols will be TR:TREATMENT_SUMMARY approved by the Penn State College of Medicine Institutional Animal Care and Use TR:TREATMENT_SUMMARY Committee. Drug Treatment: Mice will be treated with vehicle, naproxcinod (20 TR:TREATMENT_SUMMARY mg/kg/day) or equimolar naproxen (12.5mg/kg/day) once a day for 7 consecutive TR:TREATMENT_SUMMARY days. To avoid the stress of oral gavage or ip injections in mdx mice, drug or TR:TREATMENT_SUMMARY vehicle will be administered in a small volume of peanut butter. Most mice TR:TREATMENT_SUMMARY readily consume the dosed peanut butter within 30 min. Terminal experiments will TR:TREATMENT_SUMMARY be performed 2 hours after the final dose is consumed." #SAMPLEPREP SP:SAMPLEPREP_SUMMARY mouse quadriceps untarged metabolomics profiling #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent 1290 Infinity CH:COLUMN_NAME Waters Acquity HSS C18 (150 x 2.1mm, 1.8um) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:MS_COMMENTS - MS:INSTRUMENT_NAME Agilent 6550 QTOF MS:INSTRUMENT_TYPE QTOF MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_RESULTS_FILE ST000652_AN000990_Results.txt UNITS:intensity #END