title: Impaired myofibrillar function in the soleus muscle of mice with collagen-induced arthritis.
abstract: OBJECTIVE
  Progressive muscle weakness is a common feature in patients with rheumatoid arthritis (RA). However, little is known about whether the intrinsic contractile properties of muscle fibers are affected in RA. This study was undertaken to investigate muscle contractility and the myoplasmic free Ca2+ concentration ([Ca2+](i)) in the soleus, a major postural muscle, in mice with collagen-induced arthritis (CIA).
  
  
  METHODS
  Muscle contractility and [Ca2+](i) were assessed in whole muscle and intact single-fiber preparations, respectively. The underlying mechanisms of contractile dysfunction were assessed by investigating redox modifications using Western blotting and antibodies against nitric oxide synthase (NOS), superoxide dismutase (SOD), 3-nitrotyrosine (3-NT), carbonyl, malondialdehyde (MDA), and S-nitrosocysteine (SNO-Cys).
  
  
  RESULTS
  The tetanic force per cross-sectional area was markedly decreased in the soleus muscle of mice with CIA, and the change was not due to a decrease in the amplitude of [Ca2+](i) transients. The reduction in force production was accompanied by slowing of the twitch contraction and relaxation and a decrease in the maximum shortening velocity. Immunoblot analyses showed a marked increase in neuronal NOS expression but not in inducible or endothelial NOS expression, which, together with the observed decrease in SOD2 expression, favors peroxynitrite formation. These changes were accompanied by increased 3-NT, carbonyl, and MDA adducts content in myofibrillar proteins from the muscles of mice with CIA. Moreover, there was a significant increase in SNO-Cys content in myosin heavy-chain and troponin I myofibrillar proteins from the soleus muscle of mice with CIA.
  
  
  CONCLUSIONS
  These findings show impaired contractile function in the soleus muscle of mice with CIA and suggest that this abnormality is due to peroxynitrite-induced modifications in myofibrillar proteins.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Takashi.Yamada@ki.se
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.forename: Nicolas
authors.initials: N
authors.lastname: Place
authors.forename: Natalia
authors.initials: N
authors.lastname: Kosterina
authors.forename: Therese
authors.initials: T
authors.lastname: Ostberg
authors.forename: Shi-Jin
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Cecilia
authors.initials: C
authors.lastname: Grundtman
authors.forename: Helena
authors.initials: H
authors.lastname: Erlandsson-Harris
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
authors.forename: Birgitta
authors.initials: B
authors.lastname: Glenmark
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Bruton
authors.forename: Håkan
authors.initials: H
authors.lastname: Westerblad
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000503:physiopathology; D001835:Body Weight / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008811:Mice, Inbred DBA; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009210:Myofibrils / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000199:Actins; D030421:Peroxynitrous Acid; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D018995:Myosin Heavy Chains