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11.
Marine Baptissart Aurelie Vega Emmanuelle Martinot Silvère Baron Jean-Marc A. Lobaccaro David H. Volle 《Cellular and molecular life sciences : CMLS》2013,70(23):4511-4526
Bile acids are cholesterol metabolites that have been extensively studied in recent decades. In addition to having ancestral roles in digestion and fat solubilization, bile acids have recently been described as signaling molecules involved in many physiological functions, such as glucose and energy metabolisms. These signaling pathways involve the activation of the nuclear receptor farnesoid X receptor (FXRα) or of the G protein-coupled receptor TGR5. In this review, we will focus on the emerging role of FXRα, suggesting important functions for the receptor in steroid metabolism. It has been described that FXRα is expressed in the adrenal glands and testes, where it seems to control steroid production. FXRα also participates in steroid catabolism in the liver and interferes with the steroid signaling pathways in target tissues via crosstalk with steroid receptors. In this review, we discuss the potential impacts of bile acid (BA), through its interactions with steroid metabolism, on glucose metabolism, sexual function, and prostate and breast cancers. Although several of the published reports rely on in vitro studies, they highlight the need to understand the interactions that may affect health. This effect is important because BA levels are increased in several pathophysiological conditions related to liver injuries. Additionally, BA receptors are targeted clinically using therapeutics to treat liver diseases, diabetes, and cancers. 相似文献
12.
Marion Depla Rustem Uzbekov Christophe Hourioux Emmanuelle Blanchard Amélie Le Gouge Ludovic Gillet Philippe Roingeard 《Cellular and molecular life sciences : CMLS》2010,67(18):3151-3161
Hepatitis C virus (HCV) release is linked to the formation of lipid droplet (LD) clusters in the perinuclear area of infected
cells, induced by the core protein. We used electron microscopy (EM) to monitor and compare the number and size of LD in cells
producing the mature and immature forms of the HCV core protein, and 3D EM to reconstruct whole cells producing the mature
core protein. Only the mature protein coated the LD and induced their clustering and emergence from endoplasmic reticulum
membranes enriched in this protein. We found no particular association between LD clusters and the centrosome in reconstructed
cells. The LD clustering induced by the mature core protein was associated with an increase in LD synthesis potentially due,
at least in part, to the ability of this protein to coat the LD. These observations provide useful information for further
studies of the mechanisms involved in HCV-induced steatosis. 相似文献
13.
Deltcheva E Chylinski K Sharma CM Gonzales K Chao Y Pirzada ZA Eckert MR Vogel J Charpentier E 《Nature》2011,471(7340):602-607
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15.
Tumour biology: herceptin acts as an anti-angiogenic cocktail 总被引:20,自引:0,他引:20
Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments. 相似文献
16.
Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency 总被引:22,自引:0,他引:22
17.
Pathology: cancer cells compress intratumour vessels 总被引:1,自引:0,他引:1
The delivery of therapeutic drugs to solid tumours may be impaired by structural and functional abnormalities in blood and lymphatic vessels. Here we provide evidence that proliferating cancer cells cause intratumour vessels to compress and collapse. By reducing this compressive mechanical force and opening vessels, cytotoxic cancer treatments have the potential to increase blood perfusion, thereby improving drug delivery. 相似文献
18.
Pascale Romby Emmanuelle Charpentier 《Cellular and molecular life sciences : CMLS》2010,67(2):217-237
During the last decade, RNA molecules with regulatory functions on gene expression have benefited from a renewed interest.
In bacteria, recent high throughput computational and experimental approaches have led to the discovery that 10–20% of all
genes code for RNAs with critical regulatory roles in metabolic, physiological and pathogenic processes. The trans-acting RNAs comprise the noncoding RNAs, RNAs with a short open reading frame and antisense RNAs. Many of these RNAs act
through binding to their target mRNAs while others modulate protein activity or target DNA. The cis-acting RNAs include regulatory regions of mRNAs that can respond to various signals. These RNAs often provide the missing
link between sensing changing conditions in the environment and fine-tuning the subsequent biological responses. Information
on their various functions and modes of action has been well documented for gram-negative bacteria. Here, we summarize the
current knowledge of regulatory RNAs in gram-positive bacteria. 相似文献
19.
Bidart M Ricard N Levet S Samson M Mallet C David L Subileau M Tillet E Feige JJ Bailly S 《Cellular and molecular life sciences : CMLS》2012,69(2):313-324
Bone Morphogenetic Protein 9 (BMP9) has been recently found to be the physiological ligand for the activin receptor-like kinase
1 (ALK1), and to be a major circulating vascular quiescence factor. Moreover, a soluble chimeric ALK1 protein (ALK1-Fc) has
recently been developed and showed powerful anti-tumor growth and anti-angiogenic effects. However, not much is known concerning
BMP9. This prompted us to investigate the human endogenous sources of this cytokine and to further characterize its circulating
form(s) and its function. Analysis of BMP9 expression reveals that BMP9 is produced by hepatocytes and intrahepatic biliary
epithelial cells. Gel filtration analysis combined with ELISA and biological assays demonstrate that BMP9 circulates in plasma
(1) as an unprocessed inactive form that can be further activated by furin a serine endoprotease, and (2) as a mature and
fully active form (composed of the mature form associated with its prodomain). Analysis of BMP9 circulating levels during
mouse development demonstrates that BMP9 peaks during the first 3 weeks after birth and then decreases to 2 ng/mL in adulthood.
We also show that circulating BMP9 physiologically induces a constitutive Smad1/5/8 phosphorylation in endothelial cells.
Taken together, our results argue for the role of BMP9 as a hepatocyte-derived factor, circulating in inactive (40%) and active
(60%) forms, the latter constantly activating endothelial cells to maintain them in a resting state. 相似文献
20.
Benzinou M Creemers JW Choquet H Lobbens S Dina C Durand E Guerardel A Boutin P Jouret B Heude B Balkau B Tichet J Marre M Potoczna N Horber F Le Stunff C Czernichow S Sandbaek A Lauritzen T Borch-Johnsen K Andersen G Kiess W Körner A Kovacs P Jacobson P Carlsson LM Walley AJ Jørgensen T Hansen T Pedersen O Meyre D Froguel P 《Nature genetics》2008,40(8):943-945
Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity. 相似文献