Rabbit Anti-Human TXNIP (a.a. 101-200) Polyclonal antibody

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 mu 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 alpha-actinin and alpha 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. NEW & NOTEWORTHY Although severe iron loading is known to cause muscle oxidative stress and dysfunction, the effects of a moderate degree of systemic iron loading on muscle contractile function and biochemical responses remain unclear. This study demonstrates that a pathophysiological elevation in the skeletal muscle iron load leads to force deficits that coincide with impaired redox status, structural integrity, and lower ryanodine receptor-associated calstabin1 in the absence of muscle mass changes or oxidative damage.

Long noncoding RNAs (LncRNAs) may serve as miRNA sponges to regulate the expressions of miRNA target genes. LncRNA LINC00969 has been indicated to be upregulated in intervertebral disk degeneration. However, the regulatory mechanism of LINC00969 in intervertebral disk degeneration progression remains unclear. Differently expressed LINC00969, miR-335-3p, and thioredoxin-interacting protein (TXNIP) were determined in nucleus pulposus (NP) tissues and cells isolated from patients with intervertebral disk degeneration. The interaction between LINC00969, miR-335-3p, and TXNIP was also assessed. In this study, we demonstrated that LINC00969 was highly expressed, whereas miR-335-3p was aberrantly downregulated in NP tissues and cells of intervertebral disk degeneration patients. In addition, our results suggested that LINC00969 enhanced NP cell apoptosis. More importantly, LINC00969 was identified to function as a competitive endogenous RNA (ceRNA) for miR-335-3p to positively regulate TXNIP expression in vitro. Our study provided evidence for the cross-talk between LINC00969, miR-335-3p, and TXNIP, shedding light on the therapy for intervertebral disk degeneration. (c) 2018 IUBMB Life, 71(5):611-618, 2019