HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.06-7477comv1 21/11/2683    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Steensberg, A. Articles by Sander, M. Search for Related Content PubMed PubMed Citation Articles by Steensberg, A. Articles by Sander, M.

Nitric oxide production is a proximal signaling event controlling exercise-induced mRNA expression in human skeletal muscle

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

¹Correspondence: 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{at}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

This article has been cited by other articles:

				M. Hoene, R. Lehmann, A. M. Hennige, A. K. Pohl, H. U. Haring, E. D. Schleicher, and C. Weigert Acute regulation of metabolic genes and insulin receptor substrates in the liver of mice by one single bout of treadmill exercise J. Physiol., January 1, 2009; 587(1): 241 - 252. [Abstract] [Full Text] [PDF]

				B. K. Pedersen and M. A. Febbraio Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6 Physiol Rev, October 1, 2008; 88(4): 1379 - 1406. [Abstract] [Full Text] [PDF]