Metallothionein deficiency leads to soleus muscle contractile dysfunction following acute spinal cord injury in mice.
Metallothionein (MT) is a small molecular weight protein possessing metal binding and free radical scavenging properties. We hypothesized that MT-1/MT-2 null (MT(-/-)) mice would display exacerbated soleus muscle atrophy, oxidative injury, and contractile dysfunction compared with the response of wild-type (WT) mice following acute spinal cord transection (SCT). Four groups of mice were studied: WT laminectomy, WT transection, MT(-/-) laminectomy (MT(-/-) lami), and MT(-/-) transection (MT(-/-) trans). Laminectomy animals served as surgical controls. Mice in SCT groups experienced similar percent body mass (BM) losses at 7 days postinjury. Soleus muscle mass (MM) and MM-to-BM ratio were lower at 7 days postinjury in SCT vs. laminectomy mice, with no differences observed between strains. However, soleus muscles from MT(-/-) trans mice showed reduced maximal specific tension compared with MT(-/-) lami animals. Mean cross-sectional area (microm(2)) of type I and type IIa fibers decreased similarly in SCT groups compared with laminectomy controls, and no difference in fiber distribution was observed. Lipid peroxidation (4-hydroxynoneal) was greater in MT(-/-) trans vs. MT(-/-) lami mice, but protein oxidation (protein carbonyls) was not altered by MT deficiency or SCT. Expression of key antioxidant proteins (catalase, manganese, and copper-zinc superoxide dismutase) was similar between the groups. In summary, MT deficiency did not impact soleus MM loss, but resulted in contractile dysfunction and increased lipid peroxidation following acute SCT. These findings suggest a role of MT in mediating protective adaptations in skeletal muscle following disuse mediated by spinal cord injury.
DeRuisseau
Lara R
LR
Department of Biology, Le Moyne College, Syracuse, New York 13244, USA.
Recca
Daniel M
DM
Mogle
Jacqueline A
JA
Zoccolillo
Michelle
M
DeRuisseau
Keith C
KC
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D007796:Laminectomy; D015227:Lipid Peroxidation; D008297:Male; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress; D050050:Protein Carbonylation; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013904:Thoracic Vertebrae / Q000601:surgery
D000975:Antioxidants; C491054:Mt2 protein, mouse; D008668:Metallothionein; D002374:Catalase; D013482:Superoxide Dismutase