4.1 Article

Immobilization induces nuclear accumulation of HDAC4 in rat skeletal muscle

Journal

JOURNAL OF PHYSIOLOGICAL SCIENCES
Volume 66, Issue 4, Pages 337-343

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s12576-015-0432-1

Keywords

Disuse muscle atrophy; Histone deacetylase 4; Myogenic regulatory factors; Nuclear abundance

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Funding

  1. Japan Society for the Promotion of Science (JSPS) KAKENHI Grant [26506021]
  2. MEXT
  3. Grants-in-Aid for Scientific Research [15K01392, 26506021] Funding Source: KAKEN

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The study described herein aimed to examine changes in HDAC4 and its downstream targets in immobilization-induced rat skeletal muscle atrophy. Eleven male Wistar rats were used, and one hindlimb was immobilized in the plantar flexion position using a plaster cast. The contralateral, non-immobilized leg served as an internal control. After 10 days, the gastrocnemius muscles were removed from both hindlimbs. Ten days of immobilization resulted in a significant reduction (-27.3 %) in gastrocnemius muscle weight. A significant decrease in AMPK phosphorylation was also observed in nuclear fractions from immobilized legs relative to the controls. HDAC4 expression was significantly increased in immobilized legs in both the cytoplasmic and nuclear fractions. Moreover, Myogenin and MyoD mRNA levels were upregulated in immobilized legs, resulting in increased Atrogin-1 mRNA expression. Our data suggest that nuclear HDAC4 accumulation is partly related to immobilization-induced muscle atrophy.

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