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51.
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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic compound of cigarette smoke that generates electrophilic
intermediates capable of damaging DNA. Recently, we have shown that NNK can modulate mediator production by alveolar macrophages
(AM) and bronchial and alveolar epithelial cells, suggesting that cigarette smoke can alter lung immune response. Thus, we
investigated the effect of NNK and cigarette smoke extract (CSE) on AM capacity to eliminate tumoral cells. Rat AM cell line,
NR8383, was treated with NNK (500 μM) or CSE (3%) and stimulated with lipopolysaccharide (10 ng/ml). The release of cytotoxic
mediators, tumor necrosis factor (TNF) and reactive oxygen species (ROS), was measured in cell-free supernatants using ELISA
and superoxide anion production. TNF- and ROS-dependent cytotoxicity were studied using a 51Chromium-release assay and WEHI-164 and P-815 cell lines. Treatment of AM with NNK and CSE for 18 h significantly inhibited
AM TNF release. CSE exposure resulted in a significant increase of ROS production, whereas NNK did not. TNF-dependent cytotoxic
activity of NR8383 and freshly isolated rat AM was significantly inhibited after treatment with NNK and CSE. Interestingly,
although ROS production was stimulated by CSE and not affected by NNK, CSE inhibited AM ROS-dependent cytotoxicity. These
results suggest that NNK may be one of the cigarette smoke components responsible for the reduction of pulmonary cytotoxicity.
Thus, NNK may have a double pro-carcinogenic effect by contributing to DNA adduct formation and inhibiting AM cytotoxicity
against tumoral cells. 相似文献
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In parasites, host specificity may result either from restricted dispersal capacity or from fixed coevolutionary host-parasite adaptations. Knowledge of those proximal mechanisms leading to particular host specificity is fundamental to understand host-parasite interactions and potential coevolution of parasites and hosts. The relative importance of these two mechanisms was quantified through infection and cross-infection experiments using mites and bats as a model. Monospecific pools of parasitic mites (Spinturnix myoti and S. andegavinus) were subjected either to individual bats belonging to their traditional, native bat host species, or to another substitute host species within the same bat genus (Myotis). The two parasite species reacted differently to these treatments. S. myoti exhibited a clear preference for, and had a higher fitness on, its native host, Myotis myotis. In contrast, S. andegavinus showed no host choice, although its fitness was higher on its native host M. daubentoni. The causal mechanisms mediating host specificity can apparently differ within closely related host-parasite systems. 相似文献
55.
ER–mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem‐like cells 下载免费PDF全文
Valentina Chiusolo Guillaume Jacquemin Emma Boydell Sebastian Zamorano Cristina Riccadonna Serena Pellegatta Nicolas Hulo Valérie Dutoit Madiha Derouazi Pierre Yves Dietrich Paul R Walker Denis Martinvalet 《The EMBO journal》2017,36(11):1493-1512
Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem‐like cells (GSC) being more sensitive to cytotoxic lymphocyte‐mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER–mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER–mitochondria contacts compared to GDCs. Forced ER–mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER–mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. 相似文献
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NAD(P)H:nitrate reductase (NaR, EC 1.7.1.1-3) is a useful enzyme in biotechnological applications, but it is very complex in structure and contains three cofactors-flavin adenine dinucleotide, heme-Fe, and molybdenum-molybdopterin (Mo-MPT). A simplified nitrate reductase (S-NaR1) consisting of Mo-MPT-binding site and nitrate-reducing active site was engineered from yeast Pichia angusta NaR cDNA (YNaR1). S-NaR1 was cytosolically expressed in high-density fermenter culture of methylotrophic yeast Pichia pastoris. Total amount of S-NaR1 protein produced was approximately 0.5 g per 10 L fermenter run, and methanol phase productivity was 5 microg protein/g wet cell weight/h. Gene copy number in genomic DNA of different clones showed direct correlation with the expression level. S-NaR1 was purified to homogeneity in one step by immobilized metal affinity chromatography (IMAC) and total amount of purified protein per run of fermentation was approximately 180 mg. Polypeptide size was approximately 55 kDa from electrophoretic analysis, and S-NaR1 was mainly homo-tetrameric in its active form, as shown by gel filtration. S-NaR1 accepted electrons efficiently from reduced bromphenol blue (kcat = 2081 s(-1)) and less so from reduced methyl viologen (kcat = 159 s(-1)). The nitrate KM for S-NaR1 was 30 +/- 3 microM, which is very similar to YNaR1. S-NaR1 is capable of specific nitrate reduction, and direct electric current, as shown by catalytic nitrate reduction using protein film cyclic voltammetry, can drive this reaction. Thus, S-NaR1 is an ideal form of this enzyme for commercial applications, such as an enzymatic nitrate biosensor formulated with S-NaR1 interfaced to an electrode system. 相似文献
59.
Chatel G Montiel G Pré M Memelink J Thiersault M Saint-Pierre B Doireau P Gantet P 《Journal of experimental botany》2003,54(392):2587-2588
60.
Chazaud B Sonnet C Lafuste P Bassez G Rimaniol AC Poron F Authier FJ Dreyfus PA Gherardi RK 《The Journal of cell biology》2003,163(5):1133-1143
Once escaped from the quiescence niche, precursor cells interact with stromal components that support their survival, proliferation, and differentiation. We examined interplays between human myogenic precursor cells (mpc) and monocyte/macrophages (MP), the main stromal cell type observed at site of muscle regeneration. mpc selectively and specifically attracted monocytes in vitro after their release from quiescence, chemotaxis declining with differentiation. A DNA macroarray-based strategy identified five chemotactic factors accounting for 77% of chemotaxis: MP-derived chemokine, monocyte chemoattractant protein-1, fractalkine, VEGF, and the urokinase system. MP showed lower constitutive chemotactic activity than mpc, but attracted monocytes much strongly than mpc upon cross-stimulation, suggesting mpc-induced and predominantly MP-supported amplification of monocyte recruitment. Determination of [3H]thymidine incorporation, oligosomal DNA levels and annexin-V binding showed that MP stimulate mpc proliferation by soluble factors, and rescue mpc from apoptosis by direct contacts. We conclude that once activated, mpc, which are located close by capillaries, initiate monocyte recruitment and interplay with MP to amplify chemotaxis and enhance muscle growth. 相似文献