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Recent Abstracts

Variation in the adaptive response to oxidative stress with age and fiber type in mouse skeletal muscle

David J. Marcinek1,2, Jason Villarin1, Michael Siegel1, Gary Knowels1, Holly Van Remmen3 and Shane Kruse1. Radiology1, Bioengineering2, University of Washington, Seattle, WA USA 98125, Cell and Structural Biology3, University of Texas Health Sciences Center, San Antonio, TX 15355

The role of reactive oxygen species (ROS) in cellular damage has received a great deal of attention. However, ROS are also important signaling molecules involved in adaptive responses in cell energy metabolism. We test the hypothesis that the effects of oxidative stress on mitochondrial metabolism vary with age and fiber type. We used paraquat (PARA) treatment and Cu,Zn-superoxide dismutase knockout mice (SOD1) to induce acute and chronic oxidative stress, respectively, to compare the responses in soleus (sol, slow-twitch) and extensor digitorum longus (edl, fast-twitch) muscles from mice. We found a significant decline in state 3 respiration in the edl of 27mo mice 1 week after treatment with 30 mg/kg PARA. In 4 mo mice PARA treatment resulted in a trend toward increasing state 3 respiration in the edl. In contrast, there was no effect of PARA treatment on mitochondrial respiration in young or old sol. Microarray analysis of young SOD1 indicated a greater transcriptional response to the absence of SOD1 in the edl than in the sol, including genes associated with mitochondrial redox reactions and glutathione metabolism. Our results indicate that fast-twitch muscle is more susceptible to oxidative stress induced changes in mitochondrial metabolism and that these effects are qualitatively different in young and old muscle. Supported by NIH grants AG028455, AG022385, and the Ellison Medical Foundation.