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Regulated in Development and DNA Damage 1 (REDD1) Alters the Expression of a Distinct Set of Genes in Skeletal Muscle by Activity/Inactivity
Author(s) -
Gordon Bradley Scott,
Steiner Jennifer Lynn,
Williamson David,
Coen Paul,
Rossetti Michael,
Shyamalagovindarajan Subramaniam,
Eroshkin Alexey
Publication year - 2017
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.31.1_supplement.1083.2
Subject(s) - skeletal muscle , gene expression , biology , aerobic exercise , gene , endocrinology , medicine , genetics
Regulated in Development and DNA Damage 1 (REDD1) is a stress induced protein implicated in a variety of physiological and pathological conditions. While the most highly characterized role of REDD1 is its regulation of signaling through the mechanistic target of rapamycin in complex 1, recent work indicates that REDD1 may also act to modulate gene expression patterns in skeletal muscle. Interestingly, REDD1 expression is highly induced in skeletal muscle following a single bout of aerobic exercise; a stimulus known to alter gene expression. To shed further light on the consequence of REDD1 expression by activity/inactivity, REDD1+/+ and REDD1−/− mice were randomized to remain sedentary or subjected to a single bout of aerobic treadmill exercise. Mice subjected to exercise were allowed to recover for 1, 3, or 6 hr. In the plantaris of REDD1+/+ mice, REDD1 protein expression increased 907% and 201% at 1 hr and 3 hr post exercise, respectively, before returning to near baseline levels 6 hrs post exercise. As REDD1 induction was greatest 1 hr post exercise, total RNA of the plantaris from sedentary and 1 hr post exercise REDD1+/+ and REDD1−/− mice was subjected to microarray analysis. Comparison of the gene expression patterns in the muscle of sedentary mice identified 201 genes that were differentially expressed by disruption of REDD1. Specifically, qRT‐PCR analysis confirmed that the gene expression of Park2 and Ucp1, genes implicated in mitophagy and oxidative phosphorylation, were reduced by 50% and 84%, respectively, by the disruption of REDD1. Interestingly, following a bout of exercise, the microarray detected REDD1 as the gene with the greatest exercise‐induced magnitude of change in REDD1+/+ mice. Further analysis of genes altered by the absence of REDD1 in the plantaris of exercised mice revealed significant changes in 23 genes with functions related to muscle endurance, inflammation, and muscle metabolism. Subsequent qRT‐PCR analysis confirmed that the gene expression of Malt1 and Orm1 were decreased by 47% and 53%, respectively, while the gene expression of Arrdc3 was enhanced by 93% by disruption of REDD1 1 hr post exercise. Despite changes in these genes, qRT‐PCR confirmed that the induction of Peroxisome Proliferator Activated Receptor Gamma Coactivator 1 alpha (PGC‐1α), a well‐known gene induced by exercise, was unaffected by the loss of REDD1. In all, these data support a role for REDD1 in the regulation of a distinct set of genes by activity/inactivity. Support or Funding Information NIH grant F32 AA023422 (JLS)