Isolated mitochondria are well-established sources of oxidants in vitro. There is little direct evidence that mitochondria promote oxidative stress in vivo, however. Model system studies demonstrate that ortho-tyrosine, meta-tyrosine, and o,o4-dityrosine increase in proteins oxidized by hydroxyl radical. To determine whether mitochondria generate oxidants in vivo, we used isotope dilution gas chromatography-mass spectrometry to quantify levels of these markers in heart muscle of control and exercised rats. Exercise led to a 50 % increase in ortho-tyrosine, meta-tyrosine, and o,o4-dityrosine in the mitochondrial proteins but not cytosolic proteins of heart muscle. This increase was transient, and levels returned to normal when exercised animals were allowed to rest. There also was a transient increase in the level of o,o4-dityrosine in the urine of exercised rats. This relationship between mitochondrial and urine levels of o,o4-dityrosine suggests that urine assays o f this oxi dized amino acid might serve as noninvasive measures of oxidative stress. Our observations also provide direct evidence that heart muscle mitochondria produce an intermediate resembling the hydroxyl radical that promotes protein oxidation in vivo.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-25
Application #
6486735
Study Section
Project Start
2001-08-01
Project End
2002-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
25
Fiscal Year
2001
Total Cost
$157,506
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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