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REDD1 Alters the Rate of Muscle Hypertrophy following Functional Overload
Author(s) -
Gordon Bradley Scott,
Nader Gustavo,
Steiner Jennifer L,
Jefferson Leonard S,
Kimball Scot R
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1009.3
Subject(s) - muscle hypertrophy , medicine , endocrinology , skeletal muscle , phosphorylation , protein biosynthesis , mtorc1 , chemistry , biology , microbiology and biotechnology , biochemistry , protein kinase b
Overload‐induced skeletal muscle hypertrophy is due to an accretion of muscle protein, however the events that initiate the response are poorly understood. We recently showed that expression of Regulated in Development and DNA Damage 1 (REDD1), a repressor of signaling through the mechanistic target of rapamycin in complex 1 (mTORC1), significantly reduces the rate of protein synthesis following an acute bout of high frequency muscle contractions. However, it is unknown whether REDD1 expression alters the rate of overload‐induced muscle hypertrophy. To address this question, REDD1+/+ and REDD1−/− mice were subjected to unilateral functional overload (OV) of the plantaris by removal of the synergists while the contralateral sham leg served as an internal control. Mice were allowed to recover for 3 or 5 days. After 3 days of OV, mice were fasted for 16 hr, and puromycin was injected 30 min prior to sacrifice for measurement of the rate of protein synthesis. The percent increase in plantaris wet weight relative to sham was significantly greater in REDD1−/− mice at both time points which was due to increased protein content. Further examination of the early events after 3 days of OV revealed a similar rate of protein synthesis between genotypes despite increased mTORC1 activation in the REDD1−/− mice compared to controls (phosphorylation of p70S6K1 (Thr389) and 4E‐BP1 (Ser65)). Additionally, the increase in RNA content as well as the content of the 45S pre‐rRNA was not different between genotypes after 3 days OV. There was also no difference in the content of ubiquinated proteins between genotypes. These data suggest REDD1 expression regulates muscle mass following OV due to initiating events that occur prior to 3 day of OV. Support or Funding Information Supported by NIH grant DK15658 (LSJ)