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J Appl Physiol 101: 151-163, 2006. First published February 16, 2006; doi:10.1152/japplphysiol.00392.2005
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Activation pattern of MAPK signaling in the hearts of trained and untrained rats following a single bout of exercise

Motoyuki Iemitsu,1,3 Seiji Maeda,1,3 Subrina Jesmin,2,3 Takeshi Otsuki,3 Yoshitoshi Kasuya,4 and Takashi Miyauchi2,3

1Institute of Health and Sport Sciences, 2Cardiovascular Division, Institute of Clinical Medicine, and 3Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki; and 4Graduate School of Medicine, Chiba University, Inohana, Chiba, Japan

Submitted 8 April 2005 ; accepted in final form 13 February 2006

Since exercise training causes cardiac hypertrophy and a single bout induces mechanical stress to the heart, the present study aimed to characterize the activation patterns of multiple MAPK signaling pathways in the heart after a single bout of exercise or chronic exercises. The hearts of untrained rats received 5, 15, and 30 min of treadmill running exercise (Ex5 to Ex30) and rested for 0.5, 1, 3, 6, 12, and 24 h (PostEx0.5 to PostEx24) before subjecting them to the following different experiments. Activation of MAPKs (ERK, JNK, and p38) and MAPKKs (MEK1/2, SEK, and MKK3/6) increased immediately after acute exercise in a time-dependent manner, with ERK, JNK, and p38 peaking at Ex15, Ex15, and Ex30, respectively. Expression of immediate early genes (c-fos, c-jun, and c-myc) was augmented and activator protein-1 DNA binding activity was enhanced in untrained rats immediately after a single bout of exercise. The elevated levels of MAPKs declined to the resting levels within 24 h after exercise. In another set of experiments, following 4, 8, and 12 wk of exercise training, the rats exhibited significant cardiac hypertrophy by week 12. Activation of MAPKs in the 4-wk-trained rats increased after a 30-min single bout of exercise but decreased in the 8-wk group. Finally, the activity of MAPKs signaling in the 12-wk-trained rats exposed to an acute bout of exercise was unaltered. We conclude that exercise induces the activation of multiple MAPK (ERK, JNK, and p38) pathways in the heart, an effect that gradually declines with the development of exercise-induced cardiac hypertrophy.

cardiac hypertrophy; extracellular signal-regulated kinase; c-Jun NH2-terminal kinase; p38; treadmill running


Address for reprint requests and other correspondence: T. Miyauchi, Cardiovascular Division, Inst. of Clinical Medicine, Univ. of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan (e-mail: t-miyauc{at}md.tsukuba.ac.jp)




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