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

• Published in: The FASEB journal 2007-09, Vol.21 (11), p.2683-2694
• Main Authors: Steensberg, Adam, Keller, Charlotte, Hillig, Thore, Frøsig, Christian, Wojtaszewski, Jørgen F. P., Pedersen, Bente Klarlund, Pilegaard, Henriette, Sander, Mikael
• Format: Article
• Language: English
• Subjects: Adult; AMP-Activated Protein Kinases; AMP‐activated kinase; Biopsy; Enzyme Activation; Exercise - physiology; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Humans; interleukin; Interleukin-6 - genetics; Interleukin-6 - metabolism; Interleukin-8 - genetics; Interleukin-8 - metabolism; Male; Multienzyme Complexes - metabolism; Muscle, Skeletal - metabolism; NF-kappa B - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - metabolism; nuclear factor kappa B; Protein Transport; Protein-Serine-Threonine Kinases - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Thigh
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.06-7477com

Previous studies have described the magnitude and time course by which several genes are regu‐lated within exercising skeletal muscle. These include interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), heme oxygen‐ase‐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 realtime 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 con‐comitant NO synthase inhibition (nitro‐L‐arginine methyl ester, L‐NAME, 5 mgkg_1);or 2) before and after 2 h femoral artery infusion of the NO donor nitroglycerin (NTG, 1.5 μgkg_1min_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., Frosig, 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. FASEB J. 21, 2683–2694 (2007)