TY - JOUR
T1 - Regulation of mitochondrial uncoupling respiration during exercise in rat heart
T2 - Role of reactive oxygen species (ROS) and uncoupling protein 2
AU - Bo, Hai
AU - Jiang, Ning
AU - Ma, Guodong
AU - Qu, Jinting
AU - Zhang, Guizhong
AU - Cao, Dongning
AU - Wen, Li
AU - Liu, Shusen
AU - Ji, Li Li
AU - Zhang, Yong
N1 - Funding Information:
This work was supported by research grants from the National Natural Sciences Foundation of China (NNSF) (Nos. 30270638 and 30470837) and the Tianjin Scientific Research Foundation (TSRF) (No. 05YFGDS02100).
PY - 2008/4/1
Y1 - 2008/4/1
N2 - The physiological significance of cardiac mitochondrial uncoupling protein 2 (UCP2)-mediated uncoupling respiration in exercise is unknown. In the current study, mitochondrial respiratory function, UCP2 mRNA level, UCP2-mediated respiration (UCR), and reactive oxygen species (ROS) generation, as well as manganese superoxide dismutase (MnSOD) activity were determined in rat heart with or without endurance training after an acute bout of exercise of different duration. In the untrained rats, state 4 respiration and UCR-independent respiration rates were progressively increased with exercise time and were 64 and 70% higher, respectively, than resting rate at 150 min, whereas UCR was elevated by 86% with no significant change in state 3 respiration. UCP2 mRNA level showed a 5- and 4-fold increase, respectively, after 45 and 90 min of exercise, but returned to resting level at 120 and 150 min. Mitochondrial ROS production and membrane potential (Δψ) increased progressively until 120 min, followed by a decrease to the resting level at 150 min. MnSOD mRNA abundance showed a 2-fold increase at 120 min but MnSOD activity did not change with exercise. Training significantly increased mitochondrial ATP synthetase activity, ADP to oxygen consumption (P/O) ratio, respiratory control ratio, and MnSOD activity, whereas exercise-induced state 4 respiration, UCR, ROS production, and Δψ were attenuated in the trained rats. We conclude that (1) UCP2 mRNA expression and activity in rat heart can be upregulated during prolonged exercise, which may reduce cross-membrane Δψ and thus ROS production; and (2) endurance training can blunt exercise-induced UCP2 and UCR, and improve mitochondrial efficiency of oxidative phosphorylation due to increased removal of ROS.
AB - The physiological significance of cardiac mitochondrial uncoupling protein 2 (UCP2)-mediated uncoupling respiration in exercise is unknown. In the current study, mitochondrial respiratory function, UCP2 mRNA level, UCP2-mediated respiration (UCR), and reactive oxygen species (ROS) generation, as well as manganese superoxide dismutase (MnSOD) activity were determined in rat heart with or without endurance training after an acute bout of exercise of different duration. In the untrained rats, state 4 respiration and UCR-independent respiration rates were progressively increased with exercise time and were 64 and 70% higher, respectively, than resting rate at 150 min, whereas UCR was elevated by 86% with no significant change in state 3 respiration. UCP2 mRNA level showed a 5- and 4-fold increase, respectively, after 45 and 90 min of exercise, but returned to resting level at 120 and 150 min. Mitochondrial ROS production and membrane potential (Δψ) increased progressively until 120 min, followed by a decrease to the resting level at 150 min. MnSOD mRNA abundance showed a 2-fold increase at 120 min but MnSOD activity did not change with exercise. Training significantly increased mitochondrial ATP synthetase activity, ADP to oxygen consumption (P/O) ratio, respiratory control ratio, and MnSOD activity, whereas exercise-induced state 4 respiration, UCR, ROS production, and Δψ were attenuated in the trained rats. We conclude that (1) UCP2 mRNA expression and activity in rat heart can be upregulated during prolonged exercise, which may reduce cross-membrane Δψ and thus ROS production; and (2) endurance training can blunt exercise-induced UCP2 and UCR, and improve mitochondrial efficiency of oxidative phosphorylation due to increased removal of ROS.
KW - Exercise
KW - Heart
KW - Mitochondria
KW - Reactive oxygen species
KW - Training
KW - Uncoupling protein 2
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U2 - 10.1016/j.freeradbiomed.2007.12.033
DO - 10.1016/j.freeradbiomed.2007.12.033
M3 - Article
C2 - 18226608
AN - SCOPUS:40949123270
SN - 0891-5849
VL - 44
SP - 1373
EP - 1381
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 7
ER -