Reactive oxygen species (ROS) have been shown to be an important contributing factor in cell damage from many types of insults, including ischemia1repurfusion, hypoxia, heat stress, etc. Antioxidants have been shown to ameliorate the harmful effects of several of these injury types. Specifically, antioxidants have been shown to preserve muscle function in fatigue and hypoxia. The long-term objective of this study will be to elucidate the mechanism behind antioxidants' improvement of muscle function.
The specific aims of the study will be to test the hypotheses that: 1) The underlying mechanism by which antioxidants protect muscle function in hypoxia is by metabolic regulation. 2) Creatine kinase plays a pivotal role in the redox sensitivity of muscle metabolism. These hypotheses will be tested in diaphragm taken from transgenic mice that are over -expressers of mitochondrial and cytosolic SOD and matched controls. The strips will be subjected to a model of hypoxia. Adenine nucleotides, creatine phosphate, and creatine kinase will be measured using HPLC and enzymatic assay techniques. Creatine kinase function will be examined using the method of Saks et al

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-ALTX-1 (03))
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Rothgeb, Ann E
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Ohio State University
Internal Medicine/Medicine
Schools of Medicine
United States
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Rivera-Santiago, Roland F; Harper, Sandra L; Zhou, Suiping et al. (2015) Solution structure of the reduced form of human peroxiredoxin-6 elucidated using zero-length chemical cross-linking and homology modelling. Biochem J 468:87-98
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