Upregulation of MHC class I in transgenic mice results in reduced force-generating capacity in slow-twitch muscle.
Expression of major histocompatibility complex (MHC) class I in skeletal muscle fibers is an early and consistent finding in inflammatory myopathies. To test if MHC class I has a primary role in muscle impairment, we used transgenic mice with inducible overexpression of MHC class I in their skeletal muscle cells. Contractile function was studied in isolated extensor digitorum longus (EDL, fast-twitch) and soleus (slow-twitch) muscles. We found that EDL was smaller, whereas soleus muscle was slightly larger. Both muscles generated less absolute force in myopathic compared with control mice; however, when force was expressed per cross-sectional area, only soleus muscle generated less force. Inflammation was markedly increased, but no changes were found in the activities of key mitochondrial and glycogenolytic enzymes in myopathic mice. The induction of MHC class I results in muscle atrophy and an intrinsic decrease in force-generation capacity. These observations may have important implications for our understanding of the pathophysiological processes of muscle weakness seen in inflammatory myopathies. Muscle Nerve, 2008.
Salomonsson
Stina
S
Department of Medicine, Rheumatology Unit, Karolinska University Hospital-Solna, CMM L8:04, Karolinska Institute, S-171 76 Stockholm, Sweden.
Grundtman
Cecilia
C
Zhang
Shi-Jin
SJ
Lanner
Johanna T
JT
Li
Charles
C
Katz
Abram
A
Wedderburn
Lucy R
LR
Nagaraju
Kanneboyina
K
Lundberg
Ingrid E
IE
Westerblad
Håkan
H
D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D001835:Body Weight / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D024981:Glycogen Phosphorylase / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018763:Muscle Fatigue / Q000235:genetics / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D053580:Muscle Strength / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation / Q000235:genetics*
D020746:Calcium Channels, L-Type; D024243:HMGB1 Protein; D015395:Histocompatibility Antigens Class I; D002950:Citrate (si)-Synthase; D024981:Glycogen Phosphorylase