The effects of β-adrenergic stimulation and exercise on NR4A3 protein expression in rat skeletal muscle

Abstract

β-Adrenergic stimulation and exercise up-regulate the mRNA expression of nuclear receptor NR4A3, which is involved in the regulation of glucose and fatty acid utilization genes in skeletal muscle. The objective of our study was to examine the effects of β-adrenergic stimulation and exercise on the expression of NR4A3 protein in rat skeletal muscle. A single subcutaneous injection of clenbuterol, which is a β2-adrenergic receptor (β2-AR) agonist, increased NR4A3 mRNA and protein expression in the fast-twitch glycolytic triceps muscle. On the other hand, an acute 3-h session of either treadmill running or swimming did not increase the NR4A3 protein level in the exercised muscle, although both treadmill running and swimming increased NR4A3 mRNA. Finally, loss of postural contractile activity because of hindlimb immobilization reduced NR4A3 mRNA and protein in the slow-twitch oxidative soleus muscle. These results suggest that: β-adrenergic stimulation up-regulates not only NR4A3 mRNA but also NR4A3 protein in fast-twitch glycolytic muscle; exercise may increase NR4A3 mRNA but not NR4A3 protein in skeletal muscle; and local postural contractile activity plays a crucial role in maintaining NR4A3 protein expression level in postural muscle.

Pronounced Effects of Acute Endurance Exercise on Gene Expression in Resting and Exercising Human Skeletal Muscle

“…The most highly induced genes in the exercising leg were all members of the NR4A family, a subgroup of orphan receptors within the nuclear receptor superfamily. NR4A1 and NR4A3 have been reported to be upregulated shortly after acute exercise and during recovery in rat [40], [41], pig [23], and human [24], and this upregulation likely occurs locally by contractile stimuli [40]. This finding was confirmed by our study in which we observed an upregulation of NR4As in the exercising, but not in the non-exercising leg.…”

Muscle Plasticity and β2‐Adrenergic Receptors: Adaptive Responses of β2‐Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy

“…Pearen et al [36, 37] and Kawasaki et al [38] identified that β 2 -AR activation increases the expression of the orphan nuclear receptor, NOR-1 (NR4A3), a negative regulatory factor of myostatin (a member of the transforming growth factor- β superfamily and a potent negative regulator of muscle mass), in fast-twitch muscles without altering that in slow-twitch muscles. Furthermore, Shi et al [32] demonstrate the possibility that β 2 -adrenergic agonist-induced fiber-type-dependent hypertrophy is in part due to the extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) pathway.…”

Attenuating effects of clenbuterol, β₂-agonist, on immobilization - induced atrophy of rat hindlimb muscle fibers

“…Furthermore, many studies have suggested that β2-AR signaling pathways of synthesis and degradation of protein are different between fast and slow muscles, and that this agonist induces hypertrophy in fast muscles rather than in slow muscles [30][31][32][33][34] . These results suggest that the effects of β2-AR stimulation with CLE differed between fast and slow muscles, and that the hypertrophy induced by this agonist occurred more clearly in fast muscles than in slow muscles.…”