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

Lara R. DeRuisseau, Daniel M. Recca, Jacqueline A. Mogle, Michelle Zoccolillo, Keith C. DeRuisseau

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 (μm2) 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.

Original languageEnglish (US)
Pages (from-to)R1795-R1802
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume297
Issue number6
DOIs
StatePublished - Dec 2009

Keywords

  • Antioxidant
  • Muscle atrophy
  • Oxidative stress
  • Spinal cord transection
  • Stress protein

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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