Nitric oxide production is a proximal signaling event controlling exercise-induced mRNA expression in human skeletal muscle Adam Steensberg, Charlotte Keller, Thore Hillig, Christian Frøsig, Jørgen F. P. Wojtaszewski, Bente Klarlund Pedersen, Henriette Pilegaard and Mikael Sander 1 Centre of Inflammation and Metabolism, Department of Infectious Diseases, Copenhagen Muscle Research Centre and Aviation Medicine, Department of Cardiology, National Hospital, and Departments of Molecular Biology and Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark 1 Correspondence: Copenhagen Muscle Research Centre, and Aviation Medicine, Department of Cardiology, National Hospital, Section 7522, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark, Copenhagen. E-mail: sanders@dadlnet.dk Previous studies have described the magnitude and time course by which several genes are regulated within exercising skeletal muscle. These include interleukin-6 (IL-6), interleukin-8 (IL-8), heme oxygenase-1 (HO-1), and heat shock protein-72 (HSP72), which are involved in secondary signaling and preservation of intracellular environment. However, the primary signaling mechanisms coupling contraction to transcription are unknown. We hypothesized that exercise-induced nitric oxide (NO) production is an important signaling event for IL-6, IL-8, HO-1, and HSP72 expression in muscle. Twenty healthy males participated in the study. By real-time PCR, mRNA levels for 11 genes were determined in thigh muscle biopsies obtained 1) before and after 2 h knee extensor exercise without (control) and with concomitant NO synthase inhibition (nitro- L -arginine methyl ester, L-NAME, 5 mg·kg –1 ); or 2) before and after 2 h femoral artery infusion of the NO donor nitroglycerin (NTG, 1.5 µg·kg –1 ·min –1 ). L-NAME caused marked reductions in exercise-induced expression of 4 of 11 mRNAs including IL-6, IL-8, and HO-1. IL-6 protein release from the study leg to the circulation increased in the control but not in the L-NAME trial. NTG infusion significantly augmented expression of the mRNAs attenuated by L-NAME. These findings advance the novel concept that NO production contributes to regulation of gene expression in muscle during exercise. Subsequently, we sought evidence for involvement of AMP-activated kinase or nuclear factor kappa B, but found none.—Steensberg, A., Keller, C., Hillig, T., Frøsig, C., Wojtaszewski, J. F. P., Pedersen, B. K., Pilegaard, H., Sander, M. Nitric oxide production is a proximal signaling event controlling exercise-induced mRNA expression in human skeletal muscle. Key Words: interleukin • NO • AMP-activated kinase • nuclear factor kappa B
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Nitric oxide production is a proximal signaling event controlling exercise-induced mRNA expression in human skeletal muscle
Steensberg, Adam; Keller, Charlotte; Hillig, Thore; Frøsig, Christian; Wojtaszewski, Jørgen F. P.; Pedersen, Bente Klarlund; Pilegaard, Henriette; Sander, Mikael
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, Volume 21 (11): 2683
Fed of American Socs for Experimental Biology – Sep 1, 2007
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