Upregulation of uncoupling protein-3 in skeletal muscle during exercise: a potential antioxidant function

Ning Jiang, Guizhong Zhang, Hai Bo, Jinting Qu, Guodong Ma, Dongning Cao, Li Wen, Shusen Liu, Li Li Ji, Yong Zhang

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Uncoupling protein-3 (UCP3) expression has been shown to increase dramatically in response to muscular contraction, but the physiological significance of UCP3 upregulation is still elusive. In this study, UCP3 mRNA and protein expression were investigated along with mitochondrial respiratory function, reactive oxygen species (ROS) generation, and antioxidant defense in rat skeletal muscle during and after an acute bout of prolonged exercise. UCP3 mRNA expression was elevated sharply at 45 min of exercise, reaching 7- to 8-fold above resting level at 150 min. The increase in UCP3 protein content showed a latent response but was elevated ∼ 1.9-fold at 120 min of exercise. Both UCP3 mRNA and UCP3 protein gradually returned to resting levels 24 h postexercise. Mitochondrial ROS production was progressively increased during exercise. However, ROS showed a dramatic drop at 150 min although their levels remained severalfold higher during the recovery. Mitochondrial State 4 respiration rate was increased by 46 and 58% (p < 0.05) at 90 and 120 min, respectively, but returned to resting rate at 150 min, when State 3 respiration and respiratory control index (RCI) were suppressed. ADP-to-oxygen consumption (P/O) ratio and ATP synthase activity were lowered at 3 h postexercise, whereas proton motive force and mitochondrial malondialdehyde content were unchanged. Manganese superoxide dismutase gene expression was not affected by exercise except for an increase in mRNA abundance at 3 h postexercise. These data demonstrate that UCP3 expression in rat skeletal muscle can be rapidly upregulated during prolonged exercise, possibly owing to increased ROS generation. Increased UCP3 may partially alleviate the proton gradient across the inner membrane, thereby reducing further ROS production by the electron transport chain. However, prolonged exercise caused a decrease in energy coupling efficiency in muscle mitochondria revealed by an increased respiration rate due to proton leak (State 4/State 3 ratio) and decreased RCI. We thus propose that the compromise of the oxidative phosphorylation efficiency due to UCP3 upregulation may serve an antioxidant function to protect the muscle mitochondria from exercise-induced oxidative stress.

Original languageEnglish (US)
Pages (from-to)138-145
Number of pages8
JournalFree Radical Biology and Medicine
Issue number2
StatePublished - Jan 15 2009

Bibliographical note

Funding Information:
This work was supported by research grants from the National Natural Sciences Foundation of China (Nos. 30270638 and 30470837) and the Tianjin Scientific Research Foundation (No. 05YFGDSF02100).


  • Exercise
  • Free radicals
  • Manganese superoxide dismutase
  • Mitochondria
  • Reactive oxygen species
  • Skeletal muscle
  • Uncoupling protein-3


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