دورية أكاديمية
Skeletal muscle denervation causes skeletal muscle atrophy through a pathway that involves both Gadd45a and HDAC4.
| العنوان: | Skeletal muscle denervation causes skeletal muscle atrophy through a pathway that involves both Gadd45a and HDAC4. |
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| المؤلفون: | Bongers KS; Departments of Internal Medicine 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; and., Fox DK, Ebert SM, Kunkel SD, Dyle MC, Bullard SA, Dierdorff JM, Adams CM |
| المصدر: | American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2013 Oct 01; Vol. 305 (7), pp. E907-15. Date of Electronic Publication: 2013 Aug 13. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1555 (Electronic) Linking ISSN: 01931849 NLM ISO Abbreviation: Am J Physiol Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD. : American Physiological Society |
| مواضيع طبية MeSH: | Cell Cycle Proteins/*metabolism , Histone Deacetylases/*metabolism , Muscle, Skeletal/*pathology , Muscular Atrophy/*metabolism , Nuclear Proteins/*metabolism , Signal Transduction/*physiology, Activating Transcription Factor 4/genetics ; Activating Transcription Factor 4/metabolism ; Animals ; Cell Cycle Proteins/genetics ; Fasting/metabolism ; Histone Deacetylases/genetics ; Male ; Mice ; Mice, Knockout ; Muscle Denervation ; Muscle, Skeletal/innervation ; Muscle, Skeletal/metabolism ; Muscular Atrophy/genetics ; Muscular Atrophy/pathology ; Nuclear Proteins/genetics |
| مستخلص: | Skeletal muscle denervation causes muscle atrophy via complex molecular mechanisms that are not well understood. To better understand these mechanisms, we investigated how muscle denervation increases growth arrest and DNA damage-inducible 45α (Gadd45a) mRNA in skeletal muscle. Previous studies established that muscle denervation strongly induces Gadd45a mRNA, which increases Gadd45a, a small myonuclear protein that is required for denervation-induced muscle fiber atrophy. However, the mechanism by which denervation increases Gadd45a mRNA remained unknown. Here, we demonstrate that histone deacetylase 4 (HDAC4) mediates induction of Gadd45a mRNA in denervated muscle. Using mouse models, we show that HDAC4 is required for induction of Gadd45a mRNA during muscle denervation. Conversely, forced expression of HDAC4 is sufficient to increase skeletal muscle Gadd45a mRNA in the absence of muscle denervation. Moreover, Gadd45a mediates several downstream effects of HDAC4, including induction of myogenin mRNA, induction of mRNAs encoding the embryonic nicotinic acetylcholine receptor, and, most importantly, skeletal muscle fiber atrophy. Because Gadd45a induction is also a key event in fasting-induced muscle atrophy, we tested whether HDAC4 might also contribute to Gadd45a induction during fasting. Interestingly, however, HDAC4 is not required for fasting-induced Gadd45a expression or muscle atrophy. Furthermore, activating transcription factor 4 (ATF4), which contributes to fasting-induced Gadd45a expression, is not required for denervation-induced Gadd45a expression or muscle atrophy. Collectively, these results identify HDAC4 as an important regulator of Gadd45a in denervation-induced muscle atrophy and elucidate Gadd45a as a convergence point for distinct upstream regulators during muscle denervation and fasting. |
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| معلومات مُعتمدة: | I01 BX000976 United States BX BLRD VA; T32 GM007337 United States GM NIGMS NIH HHS; 1F30-AG-044964-01 United States AG NIA NIH HHS; 1R01-AR-059115-01 United States AR NIAMS NIH HHS; R01 AR059115 United States AR NIAMS NIH HHS; F30 AG044964 United States AG NIA NIH HHS |
| فهرسة مساهمة: | Keywords: activating transcription factor 4; growth arrest and DNA damage-inducible 45α; histone deacetylase 4; skeletal muscle atrophy |
| المشرفين على المادة: | 0 (Cell Cycle Proteins) 0 (Gadd45a protein, mouse) 0 (Nuclear Proteins) 145891-90-3 (Activating Transcription Factor 4) EC 3.5.1.98 (Hdac5 protein, mouse) EC 3.5.1.98 (Histone Deacetylases) |
| تواريخ الأحداث: | Date Created: 20130815 Date Completed: 20131209 Latest Revision: 20211025 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC3798708 |
| DOI: | 10.1152/ajpendo.00380.2013 |
| PMID: | 23941879 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1555 |
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| DOI: | 10.1152/ajpendo.00380.2013 |