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Publication : Metallothionein deficiency leads to soleus muscle contractile dysfunction following acute spinal cord injury in mice.

First Author  DeRuisseau LR Year  2009
Journal  Am J Physiol Regul Integr Comp Physiol Volume  297
Issue  6 Pages  R1795-802
PubMed ID  19828842 Mgi Jnum  J:226154
Mgi Id  MGI:5695844 Doi  10.1152/ajpregu.00263.2009
Citation  DeRuisseau LR, et al. (2009) Metallothionein deficiency leads to soleus muscle contractile dysfunction following acute spinal cord injury in mice. Am J Physiol Regul Integr Comp Physiol 297(6):R1795-802
abstractText  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.
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