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HO-1 Content in Skeletal Muscle and Signal Transduction.   AW von Deutsch1,2, LE Wineski4, NA Silvestrov2,3, E Simmons2,3, IK Abukhalaf5, M Bayorh1,2 and DA von Deutsch1,2,3. 1NASA Space Medicine and Life Science Research Center (SMLSRC), 2Department of Pharmacology and Toxicology, 3Clinical Research Center (CRC), 4Department of Anatomy and Neurobiology, Morehouse School of Medicine (MSM), 720 Westview Dr, SW, Atlanta, GA 30310. 5Dubai Biotechnology and Research Park (DuBiotech), Dubai, United Arab Emirates.

   Treatment with ß2-adrenernoceptor agonists (ß-ADR) results in increased levels of the polyamines spermidine and spermine predominately in fast-twitch skeletal muscles. Associated with the elevation in polyamine concentration is an attenuation of type II muscle atrophy and reduced levels of oxidative stress. Purpose: To determine whether the antioxidant enzyme heme oxygenase-1 (HO-1) is part of the signal transduction pathway mediated by polyamines. Methods: Studies were conducted using hindlimb suspended (S) and post-suspended (PS) rats. Non-suspended (NS) rats served as controls. Iron levels were determined colorimetrically. The treatment group received clenbuterol (Cb) at 1 mg/kg, while the vehicle group received normal saline. XO activity and HO-1 content were measured by kits. Results: In PS rats, plasma XO activity (p< 0.001) and mean iron content (p= 0.038) were significantly greater than NS controls. Plasma myoglobin content was significantly higher in PS rats than in NS controls. Cb-treatment resulted in higher skeletal muscle HO-1 content. Conclusions: Treatment with a ß-ADR agonist results in antioxidant protection in fast-twitch skeletal muscles through increased polyamine synthesis and HO-1 activity. In addition, the results suggest that the reloading of skeletal muscles results in increased levels of oxidative stress. This work was supported by NASA Grant NCC9-112 and NIH Grant 5P20RR011104.