Home  About us  Contact
 

B Signalling (b + signalling)

Distribution by Scientific Domains
Medical Sciences50%

Terms modified by B Signalling

  • b signalling pathway
    		•

    Selected Abstracts

    The dietary histone deacetylase inhibitor sulforaphane induces human ,-defensin-2 in intestinal epithelial cells

    IMMUNOLOGY, Issue 2 2008
    Markus Schwab
    Summary Antimicrobial peptides like human ,-defensin-2 (HBD-2) play an important role in the innate immune system protecting the intestinal mucosa against bacterial invasion. The dietary histone deacetylase (HDAC) inhibitors sulforaphane (SFN) and butyrate have received a great deal of attention because of their ability to simultaneously modulate multiple cellular targets involved in cellular protection. In this study the influence of SFN and butyrate on HBD-2 expression as well as the molecular pathways involved in SFN-mediated induction of HBD-2 were scrutinized. Treatment of Caco-2, HT-29 and SW480 cells with SFN led to a time- and dose-dependent upregulation of HBD-2 mRNA expression as determined by semi-quantitative reverse transcription,polymerase chain reaction. Moreover, HBD-2 protein production increased in response to SFN, measured by enzyme-linked immunosorbent assay. Induction of HBD-2 was also observed in response to butyrate. Immunofluorescence analysis revealed that the protein was localized in the cytosol. Coincubation of SFN with a vitamin D receptor (VDR), or an extracellular-regulated kinase 1/2 or a nuclear factor-,B inhibitor all reduced HBD-2 mRNA upregulation. In contrast, transfection of cells with a dominant-negative peroxisome proliferator-activated receptor , (PPAR,) mutant vector to inhibit PPAR, wild-type action and inhibition of p38 mitogen-activated protein kinase (MAPK) signalling did not affect SFN-mediated upregulation of HBD-2 mRNA. Moreover, SFN induced the expression of VDR, PPAR, and phosphorylated ERK1/2 but did not affect p38 MAPK activation. The data clearly demonstrate for the first time that the dietary HDAC inhibitor SFN is able to induce antimicrobial peptides in colonocytes. In this process HBD-2 expression is regulated via VDR, mitogen-activated protein kinase kinase/extracellular-regulated kinase and nuclear factor-,B signalling. [source]

    17,-oestradiol up-regulates longevity-related, antioxidant enzyme expression via the ERK1 and ERK2[MAPK]/NF,B cascade

    AGING CELL, Issue 3 2005
    Consuelo Borrás
    Summary Females live longer than males. Oestrogens protect females against aging by up-regulating the expression of antioxidant, longevity-related genes such as glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD). The mechanism through which oestrogens up-regulate those enzymes remains unidentified, but may have implications for gender differences in lifespan. We show that physiological concentrations of oestradiol act through oestrogen receptors to reduce peroxide levels in MCF-7 cells (a mammary gland tumour cell line). Oestradiol increases MAP kinase (MAPK) activation as indicated by ERK1 and ERK2 phosphorylation in MCF-7 cells, which in turn activates the nuclear factor kappa B (NF,B) signalling pathways as indicated by an increase in the p50 subunit of NF,B in nuclear extracts. Blockade of MAPK and NF,B signalling reduces the antioxidant effect of oestradiol. Finally, we show that activation of MAPK and NF,B by oestrogens drives the expression of the antioxidant enzymes Mn-SOD and GPx. We conclude that oestradiol sequentially activates MAPK and NF,B following receptor activation to up-regulate the expression of antioxidant enzymes, providing a cogent explanation for the antioxidant properties of oestrogen and its effects on longevity-related genes. [source]

    Puerarin Inhibits C-Reactive Protein Expression via Suppression of Nuclear Factor ,B Activation in Lipopolysaccharide-Induced Peripheral Blood Mononuclear Cells of Patients with Stable Angina Pectoris

    BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010
    Xiangjun Yang
    In this report, we examined the ability of puerarin to modulate C-reactive protein (CRP) expression and key molecules in the nuclear factor kappa B (NF-,B) pathway to determine its molecular target. The protein and mRNA levels of CRP were determined in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells of patients with unstable angina pectoris. Also, we detected the I-,B, phosphorylation and the p65NF-,B expression in peripheral blood mononuclear cells under our experimental condition. The results indicated that puerarin inhibited the expression of the protein and mRNA levels of CRP in LPS-induced peripheral blood mononuclear cells. Subsequently, we determined that the inhibition of CRP expression was because of a dose-dependent inhibition of phosphorylation and degradation of inhibitor kappaB(I-,B), which resulted in a reduction of p65NF-,B nuclear translocation. We conclude that puerarin acts as an anti-inflammatory agent by blocking NF-,B signalling, and may possibly be developed as a useful agent for the chemoprevention of atherosclerosis. [source]

    Crystallization and preliminary X-ray crystallographic analysis of human FAF1 UBX domain

    ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2010
    Wonchull Kang
    Fas-associated factor 1 (FAF1) is a multifunctional pro-apoptotic protein that is involved in Fas-mediated apoptosis, NF-,B signalling and the ubiquitin,proteasome pathway. In the ubiquitin,proteasome pathway, FAF1 binds to the N domain of p97/VCP, a molecular chaperone that acts in complex with the proteasome, through its C-terminal UBX domain and inhibits the proteasomal protein-degradation process. In an effort to elucidate the structural basis of the function of FAF1 in modulating p97/VCP activity related to proteasomal protein degradation, crystallographic analysis of the FAF1 UBX domain and the p97/VCP N domain was initiated. Following the recently reported crystallization of the FAF1 UBX domain bound to the p97/VCP N domain, the unbound FAF1 UBX domain was also crystallized for purposes of structural comparison. X-ray data were collected to 3.00,Å resolution and the crystals belonged to space group F4132, with unit-cell parameters a = b = c = 176.40,Å. The Matthews coefficient and solvent content were estimated to be 3.04,Å3,Da,1 and 59.5%, respectively, assuming that the asymmetric unit contained two molecules of the UBX domain, which was subsequently confirmed by molecular-replacement calculations. [source]