دورية أكاديمية
أعرض في EDS

Stress-induced skeletal muscle Gadd45a expression reprograms myonuclei and causes muscle atrophy.

التفاصيل البيبلوغرافية
العنوان: Stress-induced skeletal muscle Gadd45a expression reprograms myonuclei and causes muscle atrophy.
المؤلفون: Ebert SM; Department of and Molecular Physiology and Biophysics and Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA., Dyle MC, Kunkel SD, Bullard SA, Bongers KS, Fox DK, Dierdorff JM, Foster ED, Adams CM
المصدر: The Journal of biological chemistry [J Biol Chem] 2012 Aug 10; Vol. 287 (33), pp. 27290-301. Date of Electronic Publication: 2012 Jun 12.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
مواضيع طبية MeSH: Gene Expression Regulation* , Stress, Physiological*, Cell Cycle Proteins/*metabolism , Cell Nucleus/*metabolism , Muscle Proteins/*metabolism , Muscle, Skeletal/*metabolism , Muscular Atrophy/*metabolism , Nuclear Proteins/*metabolism, Activating Transcription Factor 4/genetics ; Activating Transcription Factor 4/metabolism ; Animals ; Cell Cycle Proteins/genetics ; Cell Line ; Cell Nucleus/genetics ; Cell Nucleus/pathology ; Energy Metabolism/genetics ; Mice ; Mice, Knockout ; Muscle Proteins/genetics ; Muscle, Skeletal/pathology ; Muscular Atrophy/genetics ; Muscular Atrophy/pathology ; Nuclear Proteins/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Protein Biosynthesis/genetics ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Signal Transduction/genetics ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factors
مستخلص: Diverse stresses including starvation and muscle disuse cause skeletal muscle atrophy. However, the molecular mechanisms of muscle atrophy are complex and not well understood. Here, we demonstrate that growth arrest and DNA damage-inducible 45a protein (Gadd45a) is a critical mediator of muscle atrophy. We identified Gadd45a through an unbiased search for potential downstream mediators of the stress-inducible, pro-atrophy transcription factor ATF4. We show that Gadd45a is required for skeletal muscle atrophy induced by three distinct skeletal muscle stresses: fasting, muscle immobilization, and muscle denervation. Conversely, forced expression of Gadd45a in muscle or cultured myotubes induces atrophy in the absence of upstream stress. We show that muscle-specific ATF4 knock-out mice have a reduced capacity to induce Gadd45a mRNA in response to stress, and as a result, they undergo less atrophy in response to fasting or muscle immobilization. Interestingly, Gadd45a is a myonuclear protein that induces myonuclear remodeling and a comprehensive program for muscle atrophy. Gadd45a represses genes involved in anabolic signaling and energy production, and it induces pro-atrophy genes. As a result, Gadd45a reduces multiple barriers to muscle atrophy (including PGC-1α, Akt activity, and protein synthesis) and stimulates pro-atrophy mechanisms (including autophagy and caspase-mediated proteolysis). These results elucidate a critical stress-induced pathway that reprograms muscle gene expression to cause atrophy.
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معلومات مُعتمدة: I01 BX000976 United States BX BLRD VA; T32 HL007121 United States HL NHLBI NIH HHS; HL007121 United States HL NHLBI NIH HHS; T32 GM07361 United States GM NIGMS NIH HHS; T32 GM007337 United States GM NIGMS NIH HHS; 1R01AR059115-01 United States AR NIAMS NIH HHS; R01 AR059115 United States AR NIAMS NIH HHS
المشرفين على المادة: 0 (Atf4 protein, mouse)
0 (Cell Cycle Proteins)
0 (Gadd45a protein, mouse)
0 (Muscle Proteins)
0 (Nuclear Proteins)
0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
0 (Ppargc1a protein, mouse)
0 (RNA, Messenger)
0 (Trans-Activators)
0 (Transcription Factors)
145891-90-3 (Activating Transcription Factor 4)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
تواريخ الأحداث: Date Created: 20120614 Date Completed: 20121105 Latest Revision: 20211021
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC3431665
DOI: 10.1074/jbc.M112.374777
PMID: 22692209
قاعدة البيانات: MEDLINE
الوصف
تدمد:1083-351X
DOI:10.1074/jbc.M112.374777