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The M ycobacterium tuberculosis genome encodes five putative 'alternative' ribosomal proteins whose expression is repressed at high Zn2+ concentration. Each alternative protein has a primary homologue that is predicted to bind Zn2+. We hypothesized that zinc triggers a switch between these paired homologous proteins and therefore chose one of these pairs, S18-1/ S18-2, to study mechanisms of the predicted competition for their incorporation into ribosomes. Our data show that Zn2+-depletion causes accumulation of both S18-2 mRNA and protein. In contrast, S18-1 mRNA levels are unchanged to slightly elevated under Zn2+-limited conditions. However, the amount of S18-1 protein is markedly decreased. We further demonstrate that both S18 proteins interact with ribosomal protein S6, a committed step in ribosome biogenesis. Zn2+ is absolutely required for the S18-1/ S6 interaction while it is dispensable for S18-2/ S6 dimer formation. These data suggest a model in which S18-1 is the dominant ribosome constituent in high zinc conditions, e.g. inside of phagosomes, but that it can be replaced by S18-2 when zinc is deficient, e.g. in the extracellular milieu. Consequently, Zn2+-depletion may serve as a signal for building alternative ribosomes when M . tuberculosis is released from macrophages, to allow survival in the extracellular environment. [ABSTRACT FROM AUTHOR]

It has been proposed that obesity and type 2 diabetes (T2D) are state of chronic low grade inflammation that elevates activity of proinflammatory/stress-signaling pathways. NFκB signaling pathway may play a role in the pathogenesis of insulin resistance associated with obesity and T2D. Local lipid infusion and diet-induced obesity studies show changes in the inhibitor of κB (IκB)/NFκB signaling pathway. Despite these observations, the effect of obesity per se on the activity of IκB/NF κB pathways in skeletal muscle remains unclear. Therefore, we studied the relationship between % body fat and the (IκB)/NF κB inflammation signaling pathway in skeletal muscle from 25 non-diabetic volunteers with a wide range of adiposity but similar BMI. Subjects were divided into two groups, low body fat (LBF, < 30% body fat, n=14, 3F/11 M, 25±1% fat, BMI=29±1, 35±3 yr) and high body fat group (HBF, > 30% body fat, n=11, 6F/5M, 40±2% fat [P<0.01], BMI=31±2 [P=NS], 40±3 yr [P=NS]). Insulin sensitivity was determined by euglycemic clamp (80 mU-m sup -2]min[sup -1]); IκBα, Phospho-IκB α IκB β, NF κB p50, and NF κB p65 protein were determined by immunoblot analysis. Insulin-stimulated glucose disposal was greater in LBF than HBF (5.90.4 vs 3.7 0.4 mg⋅kg[sup -1]⋅min[sup -1], P<0.01) despite similar BMI. Muscle from subjects with HBF was characterized by a 13.0±0.1 % decrease in IκBα (P < 0.001) and 15.4±0.1% increase (P < 0.03) in phospho- IκBα protein abundance, indicating activation of the IκB/NF κB pathway. IκBα (r = -0.74, P < 0.000l) and IκBα (r = -0.49, P < 0.02) protein abundance inversely correlated with % body fat while phospho- IκBα protein abundance directly correlated with % body fat (r = 0.55, P < 0.01). In summary, increased % body fat is associated with activation of IκB/NF κB signaling in skeletal muscle independent of BMI. [ABSTRACT FROM AUTHOR]