Journal of Applied Physiology AJP: Heart and Circulatory Physiology
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J Appl Physiol 99: 2271-2277, 2005. First published August 11, 2005; doi:10.1152/japplphysiol.00412.2005
8750-7587/05 $8.00
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Thiol supplementation in aged animals alters antioxidant enzyme activity after heat stress

Joanna P. Morrison,1 Mitchell C. Coleman,2 Elizabeth S. Aunan,1 Susan A. Walsh,2 Douglas R. Spitz,2 and Kevin C. Kregel1,2

1Integrative Physiology Laboratory, Department of Exercise Science, and 2Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, Iowa

Submitted 13 April 2005 ; accepted in final form 11 August 2005

Declines in oxidative and thermal stress tolerance are well documented in aging systems. It is thought that these alterations are due in part to reductions in antioxidant defenses. Although intracellular thiols are major redox buffers, their role in maintaining redox homeostasis is not completely understood, particularly during aging, where the reliance on antioxidant enzymes and proteins may be altered. To determine whether thiol supplementation improved the antioxidant enzyme profile of aged animals after heat stress, young and old Fischer 344 rats were treated with N-acetylcysteine (NAC; 4 mmol/kg ip) 2 h before heat stress. Liver tissue was collected before and 0, 30, and 60 min after heat stress. Aging was associated with a significant decline in tissue cysteine and glutathione (GSH) levels. There was also an age-related decrease in copper-zinc superoxide dismutase activity. Heat stress did not alter liver GSH, glutathione disulfide, or antioxidant enzyme activity. With NAC treatment, old animals took up more cysteine than young animals as reflected in an increase in liver GSH and a corresponding decrease in glutamate cysteine ligase activity. Catalase activity increased after NAC treatment in both age groups. Copper-zinc superoxide dismutase activity did not change with heat stress or drug treatment, whereas manganese superoxide dismutase activity was increased in old animals only. These data indicate that GSH synthesis is substrate limited in old animals. Furthermore, aged animals were characterized by large fluctuations in antioxidant enzyme balance after NAC treatment, suggesting a lack of fine control over these enzymes that may leave aged animals susceptible to subsequent stress.

reactive oxygen species; redox modulation; thiols; cysteine; hyperthermia



Address for reprint requests and other correspondence: K. C. Kregel, Integrative Physiology Laboratory, 532 FH, The Univ. of Iowa, Iowa City, IA 52242 (e-mail: kevin-kregel{at}uiowa.edu)







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