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

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL010216-01A1
Application #
6140045
Study Section
Special Emphasis Panel (ZRG1-ALTX-1 (03))
Project Start
2000-04-05
Project End
Budget Start
2000-04-05
Budget End
2001-04-04
Support Year
1
Fiscal Year
2000
Total Cost
$46,300
Indirect Cost
Name
Ohio State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
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
Palmer, Brian S; Klawitter, Paul F; Reiser, Peter J et al. (2004) Degradation of rat cardiac troponin I during ischemia independent of reperfusion. Am J Physiol Heart Circ Physiol 287:H1269-75
Klawitter, Paul F; Clanton, Thomas L (2004) Tension-time index, fatigue, and energetics in isolated rat diaphragm: a new experimental model. J Appl Physiol 96:89-95
Angelos, Mark G; Murray, Holt N; Gorsline, Robert T et al. (2002) Glucose, insulin and potassium (GIK) during reperfusion mediates improved myocardial bioenergetics. Resuscitation 55:329-36
Klawitter, Paul F; Murray, Holt N; Clanton, Thomas L et al. (2002) Low flow after global ischemia to improve postischemic myocardial function and bioenergetics. Crit Care Med 30:2542-7
Klawitter, Paul F; Murray, Holt N; Clanton, Thomas L et al. (2002) Reactive oxygen species generated during myocardial ischemia enable energetic recovery during reperfusion. Am J Physiol Heart Circ Physiol 283:H1656-61
Clanton, T L; Klawitter, P F (2001) Invited review: Adaptive responses of skeletal muscle to intermittent hypoxia: the known and the unknown. J Appl Physiol 90:2476-87