Functional and biochemical responses of skeletal muscle following a moderate degree of systemic iron loading in mice
Document Type
Article
Publication Title
Journal of Applied Physiology
Abstract
Excessive iron loading may cause skeletal muscle atrophy and weakness because of its free radical generating properties. To determine whether a clinically relevant degree of iron loading impairs skeletal muscle function, young male mice received injections of iron dextran (4 mg iron/200 l) or 2 mM D-glucose (control) 5 days/week for 2 weeks (n 10/group). Systemic iron loading induced an approximate fourfold increase in the skeletal muscle nonheme iron concentration. Soleus specific tension (1, 30 –250 Hz) was lower among iron-loaded animals compared with controls despite similar body mass and muscle mass. Soleus lipid peroxidation (4-hydroxynonenal adducts) and protein oxidation (protein carbonyls) levels were similar between groups. In gastrocnemius muscle, reduced glutathione (GSH) and glutathione peroxidase activity were similar but glutathione disulfide (GSSG) and the GSSG/GSH ratio were greater in iron-loaded muscle. A greater protein expression level of endogenous thiol antioxidant thioredoxin (TRX) was observed among iron-loaded muscle whereas its endogenous inhibitor thioredoxin-interacting protein (TXNip) and the TRX/TXNip ratio were similar. Glutaredoxin2, a thiol-disulfide oxidoreductase activated by GSSG-induced destabilization of its iron-sulfur [2Fe-2S] cluster, was lower following iron loading. Additionally, protein levels of -ac-tinin and II-spectrin at 240 kDa were lower in the iron-loaded group. Ryanodine receptor stabilizing subunit calstabin1 was also lower following iron loading. In summary, the contractile dysfunction that resulted from moderate iron loading may be mediated by a disturbance in the muscle redox balance and from changes arising from an increased proteolytic response and aberrant sarcoplasmic reticulum Ca2 release.
First Page
799
Last Page
809
DOI
10.1152/japplphysiol.00237.2018
Publication Date
1-17-2019
Recommended Citation
Liang, Chen; Mickey, Marisa C.; Receno, Candace N.; Atalay, Mustafa; and DeRuisseau, Keith C., "Functional and biochemical responses of skeletal muscle following a moderate degree of systemic iron loading in mice" (2019). Basic Sciences Faculty Publications. 34.
https://doi.org/10.1152/japplphysiol.00237.2018
https://collections.uhsp.edu/basic-sciences_pubs/34