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J Appl Physiol 106: 1826-1831, 2009. First published April 9, 2009; doi:10.1152/japplphysiol.90923.2008
8750-7587/09 $8.00
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Role of local muscle contractile activity in the exercise-induced increase in NR4A receptor mRNA expression

Emi Kawasaki, Fumi Hokari, Maiko Sasaki, Atsushi Sakai, Keiichi Koshinaka, and Kentaro Kawanaka

Department of Health and Nutrition, Niigata University of Health and Welfare, Niigata, Japan

Submitted 18 July 2008 ; accepted in final form 23 March 2009

Exercise upregulates the expression of NR4A receptors, which are involved in regulation of glucose and fatty acid utilization genes in skeletal muscle. The aims of our study were 1) to determine the role of local contractile activity on NR4A mRNA expression in skeletal muscle during exercise; and 2) to elucidate the mechanisms underlying the induction of NR4A mRNA expression in response to muscle contractile activity. Rats were subjected to an acute 3-h low-intensity swimming or a 3-h low-intensity treadmill running as a model of endurance exercise. Low-intensity swimming increased NR4A1 and NR4A3 mRNA in triceps but not in soleus muscle. Conversely, low-intensity treadmill running increased NR4A1 and NR4A3 mRNA in soleus but not in triceps muscle. NR4A mRNA increased concomitantly with reduced postexercise muscle glycogen, suggesting that gene expression of NR4A receptors occurs in muscles recruited during exercise. Furthermore, in resting rats, an acute 1-h local electrical stimulation of a motor nerve to the tibialis anterior muscle caused increases in NR4A1 and NR4A3 mRNA relative to the contralateral control muscle of the same animals. On the other hand, after 6 h of hindlimb immobilization, NR4A1 and NR4A3 mRNA were reduced in immobilized soleus muscle relative to contralateral control muscle. In addition, both NR4A1 and NR4A3 mRNA in epitrochlearis muscle were increased after 6-h incubation with 0.5 mM 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, which activates AMP-activated protein kinase. These results suggest that 1) local muscle contractile activity is required for increased expressions of NR4A1 and NR4A3 mRNA during exercise; and 2) muscle contractile activity-induced increases in NR4A1 and NR4A3 mRNA may be mediated by AMPK activation, at least in part.

swimming; treadmill running; Nur77; NOR1; electrical stimulation; immobilization; adenosine 5'-monophosphate-activated protein kinase



Address for reprint requests and other correspondence: K. Kawanaka, Dept. of Health and Nutrition, Niigata Univ. of Health and Welfare, 1398 Shimami-cho, Niigata City, Niigata 950-3198, Japan (e-mail: kawanaka{at}nuhw.ac.jp)







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