Heterogeneous nuclear ribonucleoproteins as targets of autoantibodies in systemic rheumatic diseases.
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in Arthritis and Rheumatism (2012), 64(1), 213-221
BACKGROUND: Heterogeneous nuclear ribonucleoproteins (hnRNP) are abundant nucleoplasmic pre-mRNA-binding proteins. The aim of this study was to unravel the mosaic of autoantibodies to hnRNP's in systemic ... [more ▼]
BACKGROUND: Heterogeneous nuclear ribonucleoproteins (hnRNP) are abundant nucleoplasmic pre-mRNA-binding proteins. The aim of this study was to unravel the mosaic of autoantibodies to hnRNP's in systemic rheumatic diseases. METHODS: Recombinant human hnRNP A1, B1, C1, E1, F, Gi, H1, I, K, and P2 were prepared. Antibodies to these antigens were determined by Western blotting and ELISA (for hnRNP B1, E1, F, and H1) in controls (chronic fatigue syndrome) and in patients with various connective tissue disorders. RESULTS: Western blotting analysis on 106 controls and 298 patients with a connective tissue disorder revealed that antibodies to all tested hnRNP antigens, except hnRNP Gi, were significantly more prevalent in Sjogren's syndrome (SS) than in controls. The highest reactivity was found for hnRNP B1, E1, F, and H1 (reactivity in >45% of patients with SS and in 2.8% of controls). Reactivity to hnRNP B1, E1, F, and H1 was also evaluated by ELISA in controls and in 228 patients with a connective tissue disease. Reactivity to at least 2 of the 4 tested antigens was found in 1.1% of controls, 16% of patients with systemic lupus erythematosus (SLE), and 18% of patients with SS. Reactivity to at least 3 of the 4 antigens was found in none of the controls, in 3.2% of patients with SLE, and in 15% of patients with SS. CONCLUSIONS: several hnRNP's are target antigens in SS. The combined presence of antibodies to several hnRNP's was strongly associated with connective tissue disease in general and SS in particular. [less ▲]Detailed reference viewed: 25 (14 ULg)
De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation.
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in Cancer Research (2010), 70(20), 8117-26
Activation of de novo lipogenesis in cancer cells is increasingly recognized as a hallmark of aggressive cancers and has been implicated in the production of membranes for rapid cell proliferation. In the ... [more ▼]
Activation of de novo lipogenesis in cancer cells is increasingly recognized as a hallmark of aggressive cancers and has been implicated in the production of membranes for rapid cell proliferation. In the current report, we provide evidence that this activation has a more profound role. Using a mass spectrometry-based phospholipid analysis approach, we show that clinical tumor tissues that display the lipogenic phenotype show an increase in the degree of lipid saturation compared with nonlipogenic tumors. Reversal of the lipogenic switch in cancer cells by treatment with the lipogenesis inhibitor soraphen A or by targeting lipogenic enzymes with small interfering RNA leads to a marked decrease in saturated and mono-unsaturated phospholipid species and increases the relative degree of polyunsaturation. Because polyunsaturated acyl chains are more susceptible to peroxidation, inhibition of lipogenesis increases the levels of peroxidation end products and renders cells more susceptible to oxidative stress-induced cell death. As saturated lipids pack more densely, modulation of lipogenesis also alters lateral and transversal membrane dynamics as revealed by diffusion of membrane-targeted green fluorescent protein and by the uptake and response to doxorubicin. These data show that shifting lipid acquisition from lipid uptake toward de novo lipogenesis dramatically changes membrane properties and protects cells from both endogenous and exogenous insults. These findings provide important new insights into the role of de novo lipogenesis in cancer cells, and they provide a rationale for the use of lipogenesis inhibitors as antineoplastic agents and as chemotherapeutic sensitizers. [less ▲]Detailed reference viewed: 19 (0 ULg)