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 MMto-BM ratio were lower at 7 days postinjury in SCT vs. laminectomy mice, with no differences observed between strains. However, soleus muscles from MT Ϫ/Ϫ trans mice showed reduced maximal specific tension compared with MT Ϫ/Ϫ lami animals. Mean cross-sectional area (m 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 Ϫ/Ϫ trans vs. MT Ϫ/Ϫ 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. muscle atrophy; oxidative stress; spinal cord transection; antioxidant; stress protein METALLOTHIONEIN (MT) IS A small molecular weight metal binding protein expressed as four isoforms in humans, mice, and other mammals (reviewed in Ref. 18). Metallothionein-1 (MT-1) and metallothionein-2 (MT-2) proteins are ubiquitously expressed and are inducible isoforms of MT. Conversely, metallothionein-3 (MT-3) and metallothionein-4 (MT-4) display more limited expression and are found primarily in the brain and skin, respectively. MT appears to be involved in numerous cellular processes that include free radical scavenging, intracellular zinc transport and storage, metal detoxification, and zinc exchange with metalloproteins (reviewed in Ref.

Caffeine is a pharmacological agent that has been shown to enhance muscle contraction. The stimulatory effects of caffeine may be, in part, due to alterations in the skeletal muscle redox status. Specifically, caffeine administration to rats has been shown to rapidly, but transiently, decrease levels of skeletal muscle nitric oxide (NO) synthase. Decreased levels of NO could lead to elevated oxidative stress, since NO is a potent superoxide radical scavenger. We tested the hypothesis that acute caffeine administration would decrease muscle nitrosative stress, increase oxidative stress, and upregulate the expression of key antioxidant enzymes. Male Sprague Dawley rats received i.p. administration of caffeine (16 mg/kg; n=8) or vehicle (saline; n=8). Thirty minutes post injection the rats were anesthetized and the soleus muscles were harvested for analysis. No differences in oxidative injury (protein carbonyls) or nitrosative injury (3‐nitrotyrosine) were detected (p>0.05). Caffeine administration did not alter manganese superoxide dismutase or copper‐zinc superoxide dismutase protein levels, but resulted in a 50% increase in catalase protein levels (p<0.05). In summary, acute caffeine administration may upregulate skeletal muscle catalase expression by a mechanism independent of oxidative stress. Supported by Syracuse University SOE and APS UGSRF

Metallothioneins (Mts) are small molecular weight proteins possessing metal binding and free radical scavenging properties that are upregulated in skeletal muscle following acute spinal cord injury (SCI). We tested the postulate that deficiency of Mt (Mt1 and Mt2; Mt−/−) would exacerbate the development of atrophy, contractile dysfunction, and the oxidative stress response of the soleus following SCI (7 days, T9) compared to control strain mice. Four groups of mice were studied: control transected (CT, n=12); Mt−/− transected (MT; n=12); control laminectomy (CL, n=7); and Mt−/− laminectomy (ML, n=5). CT and MT mice experienced similar % body weight losses following SCI vs. pre‐surgery values. Soleus muscle mass: body mass ratio was lower (p<.05) for CT vs. CL and MT vs. ML groups, with no difference between MT and CT groups. MT mice showed reduced maximal specific tension values at high stimulation frequencies compared to ML animals (p<.05). Furthermore, oxidative stress (4‐hydroxynoneal) and protein levels for the antioxidant catalase were greater (p<.05) in MT vs. ML, but not in CT vs. CL groups. No differences in manganese superoxide dismutase (SOD) or copper‐zinc SOD protein levels were detected between groups. In summary, Mt−/− does not impact muscle mass loss but leads to lower maximal force generating ability and increased oxidative stress of the soleus following acute SCI. Support: Syracuse University SOE

Metallothioneins (Mts) are small molecular weight proteins that possess metal binding and free radical scavenging properties. Furthermore, Mt is a stress protein that likely participates in the adaptive response of skeletal muscle to stressful stimuli and is up‐regulated following acute spinal cord injury (SCI). We tested the hypothesis that loss of Mt (Mt1 and Mt2; Mt−/ −) would lead to exacerbated atrophy and contractile dysfunction of the soleus muscle following acute SCI (7 days, T9 transection) in Mt−/ − mice compared to control strain mice. Transected control strain (CT; n=5) and transected Mt−/ − (MT; n=6) mice experienced an equivalent % loss of body weight by day 7 of recovery compared to pre‐surgery weight (CT = −8.6 ± 1.6; MT = −11.6 ± 2.4). Soleus muscle mass (mg) of CT (4.3 ± 0.2) and MT (4.6 ± 0.1) groups was lower (p<0.05) than the non‐surgical control strain (NS; n=5; 5.6 ± 0.3). However, preliminary data (n=1–3/group) indicate that a lower maximal specific tension (N/cm2) is generated by the soleus in MT vs. controls (NS=23.7 ± 2.5; CT=22.1; MT 19.0 ± 0.0). In summary, deficiency of Mt1 and Mt2 does not alter the loss of muscle mass but may lead to lower maximal force generating ability of the soleus in response to disuse resulting from spinal cord injury.Supported by Syracuse University SOE