HBx induces the proliferation of hepatocellular carcinoma cells via AP1 overexpressed by ER stress
In conclusion, in HBV-infected hepatic cells or chronic hepatitis B patients, CREBH may induce proliferation of hepatic cells in cooperation with HBx, resulting in HCC. (Source: BJ Disease)
Source: BJ Disease - November 27, 2014 Category: Biochemistry Authors: H Cho, S Kim, Y Kyaw, A Win, S Koo, H Kim, J Cheong Tags: BJ Disease Source Type: research
Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3{beta}: Auto regulation of GSK-3{beta} in vivo
Wnt/β-catenin signalling is an important pathway that regulates multiple biological processes including cell adhesion and cell fate determination during animal development and in the adult nervous system regulates the structure and function of synapses. Wnt signalling dysfunction is associated with several neurodegenerative diseases such as schizophrenia and Alzheimer´s disease. The use of natural compounds is an interesting strategy in the search of drugs with therapeutic potential to activate this signalling pathway. Here, we report that andrographolide (ANDRO), a component of Andrographis paniculata, is a ...
Source: BJ Disease - November 25, 2014 Category: Biochemistry Authors: C Tapia-Rojas, A Schüller, C B. Lindsay, R C. Ureta, C Mejías-Reyes, J Hancke, F Melo, N C. Inestrosa Tags: BJ Signal Source Type: research
Steatosis inhibits liver cell store-operated Ca2{+} entry and reduces ER Ca2{+} through a protein kinase C dependent mechanism
Lipid accumulation in hepatocytes can lead to non-alcoholic fatty liver disease, which can progress to non-alcoholic steatohepatitis and type 2 diabetes. Hormone-initiated release of Ca2+ from the endoplasmic reticulum stores and subsequent replenishment of these stores by Ca2+ entry through store-operated Ca2+ channels plays a critical role in the regulation of liver metabolism. Endoplasmic reticulum Ca2+ homeostasis is known to be altered in steatotic hepatocytes. Whether store-operated Ca2+ entry is altered in steatotic hepatocytes and mechanisms involved was investigated. Lipid accumu...
Source: BJ Disease - November 24, 2014 Category: Biochemistry Authors: C H Wilson, E S Ali, N Scrimgeour, A M Martin, J Hua, G A Tallis, G Y Rychkov, G J Barritt Tags: BJ Disease Source Type: research
The eukaryotic elongation factor eEF1A1 interacts with SAMHD1
Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), a Mendelian inflammatory disease which displays remarkable clinical and biochemical overlap with congenital viral infection. SAMHD1 has also been defined as an HIV-1 restriction-factor that, through a novel triphosphohydrolase activity, inhibits early stage HIV-1 replication in myeloid derived dendritic cells (MDDCs), macrophages and resting CD4+ T-cells. The potent activity of SAMHD1 is likely to be the subject of a variety of regulatory mechanisms. Knowledge of proteins that interact with SAMHD1 may not only enhance our understanding of the pathoge...
Source: BJ Disease - November 24, 2014 Category: Biochemistry Authors: C Morrissey, D Schwefel, V Ennis-Adeniran, I A Taylor, Y J Crow, M Webb Tags: BJ Biomolecules Source Type: research
A quantitative proteomics-based signature of platinum sensitivity in ovarian cancer cell lines
This study illustrates the importance of proteomics-based discovery for defining the basis for the carboplatin response in ovarian cancer and highlights candidate proteins, particularly involved in cellular redox regulation, homologous recombination and DNA damage repair, that otherwise could not have been predicted from whole genome and expression data sources alone. (Source: BJ Disease)
Source: BJ Disease - November 19, 2014 Category: Biochemistry Authors: G Fan, K Wrzeszczynski, C Fu, G Su, D J Pappin, R Lucito, N K Tonks Tags: BJ Signal Source Type: research
Epithelial MUC1/Muc1 Promotes Cell migration, Reduces Apoptosis and Affects Levels of Mucosal Modulators During Acetylsalicylic Acid (Aspirin) Induced Gastropathy.
MUC1 is a transmembrane mucin highly expressed in the stomach. While extensive research has uncovered many of its roles in cancer, knowledge about the functions of MUC1 in normal tissues is limited. Here we showed that acetylsalicylic acid (Aspirin, ASA) upregulated MUC1/Muc1 expression in the gastric mucosa of humans and wild type mice. ASA induced mucosal injury in all mice to a similar extent, however wild type animals and those chimeras with Muc1 on the epithelia recovered faster than Muc1 knock-out mice and chimeras carrying Muc1 on haematopoietic but not epithelial cells. MUC1 enhanced proliferation and migration of ...
Source: BJ Disease - November 11, 2014 Category: Biochemistry Authors: D Banerjee, H Robert Fernandez, P Bhatu Patil, P Premaratne, M Quiding-Järbrink, S Katarina Lindén Tags: BJ Biomolecules Source Type: research
C/EBP homologous protein (CHOP) contributes to hepatocyte death via the promotion of ERO1{alpha} signaling in acute liver failure
This study was designed to investigate the roles and molecular mechanisms of CHOP in ALF. In the liver tissues from ALF patients, the expression of CHOP was significantly increased, which accompanied by increased expression of PERK signaling, ATF6 signaling, IRE1 signaling and ERO1a, as compared with healthy controls. In the mouse model of GaIN/LPS-induced ALF, the hepatocellular injury was accompanied by upregulated PERK signaling, ATF6 signaling, IRE1 signaling, CHOP and ERO1a. In contrast, CHOP deficiency decreased hepatocellular apoptosis/necrosis and increased animal survival. Furthermore, disruption of CHOP decreased...
Source: BJ Disease - November 11, 2014 Category: Biochemistry Authors: J Rao, C Zhang, P Wang, L Lu, X Qian, J Qin, X Pan, G Li, X Wang, F Zhang Tags: BJ Disease Source Type: research
Application of a novel regulatable Cre recombinase system to define the role of liver and gut metabolism in drug oral bioavailability
The relative contribution of hepatic versus intestinal oxidative metabolism is a crucial factor in drug oral bioavailability and therapeutic efficacy. Oxidative metabolism is mediated by the cytochrome P450 mono-oxygenase system to which cytochrome P450 reductase (POR) is the essential electron donor. In order to study the relative importance of these pathways in drug disposition we have generated a novel mouse line where Cre recombinase is driven off the endogenous Cyp1a1 gene promoter; this line was then crossed into a floxed POR mouse. A 40mg/kg dose of the Cyp1a1 inducer 3-methylcholanthrene (3MC) eliminated POR expres...
Source: BJ Disease - November 7, 2014 Category: Biochemistry Authors: C J Henderson, L A McLaughlin, M Osuna-Cabello, M Taylor, I Gilbert, A W McLaren, C Roland Wolf Tags: BJ Metabolism Source Type: research
The role of Ca2{+} influx in endocytic vacuole formation in pancreatic acinar cells
In this study we investigated the relationship between the formation of endocytic vacuoles and Ca2+ influx developed in response to the inducers of acute pancreatitis ((bile acid taurolithocholic acid 3-sulfate (TLC-S) and supramaximal concentration of cholecystokinin-8 (CCK)). We found that the inhibitor of STIM/Orai channels GSK-7975A effectively suppressed both Ca2+ influx (stimulated by inducers of pancreatitis) and the formation of endocytic vacuoles. Cell death induced by TLC-S or CCK was also inhibited by GSK-7975A. We documented the formation of endocytic vacuoles in response to store-operated Ca2�...
Source: BJ Disease - November 5, 2014 Category: Biochemistry Authors: S Voronina, D Collier, M Chvanov, B Middlehurst, A J Beckett, I A. Prior, D N Criddle, M Begg, K Mikoshiba, R Sutton, A V Tepikin Tags: BJ Disease Source Type: research
A cholesterol consensus motif is required for efficient intracellular transport and raft association of a group 2 HA of influenza virus
The HA (haemagglutinin) of influenza viruses must be recruited to membrane rafts to perform its function in membrane fusion and virus budding. We previ-ously showed with Förster Resonance Energy Transfer (FRET) that deletion of the two rafttargeting features of HA, S-acylation at the cytoplasmic tail and the hydrophobic amino acids VIL in the outer part of the transmembrane region (TMR) lead to reduced raft association. In addition, exchange of VIL, but not of the S-acylation sites severely retards transport of HA through the Golgi. Here we have further characterized the ill-defined signal in the TMR. A sequence com...
Source: BJ Disease - October 21, 2014 Category: Biochemistry Authors: M De Vries, A Herrmann, M Veit Tags: BJ Biomolecules Source Type: research
The SARS-Coronavirus Membrane protein induces apoptosis via interfering PDK1-PKB/Akt signaling
In this study, we demonstrated that the C-terminus of M-protein interacts with the Pleckstrin Homology (PH) domain of PDK1. This interaction disrupted the association between PDK1 and PKB/Akt, and led to down-regulation of PKB/Akt activity. This subsequently reduced the level of phosphorylated forkhead transcription factor FKHRL1 and apoptosis signal-regulating kinase (ASK), and led to the activation of caspases 8 and 9. Altogether, our data demonstrate that SARS-CoV M-protein induces apoptosis through depriving PDK1 from interacting with PKB/Akt, and this causes the activation of apoptosis. Our work highlights the SARS-Co...
Source: BJ Disease - October 1, 2014 Category: Biochemistry Authors: H Tsoi, L Li, Z S Chen, K Lau, S Tsui, H Edwin Chan Tags: BJ Disease Source Type: research
Identification of NOX2 regions for normal biosynthesis of cytochrome b558 in phagocytes - Highlighting essential residues for p22phox binding
Cytochrome b558, the redox core of the NADPH-oxidase complex in phagocytes, is composed of NOX2 and p22phox whose synthesis are intimately connected but not fully understood. We reproduced ten rare Xminus chronic granulomatous disease mutations of highly conserved residues in NOX1–4, in the X0CGD PLB-985 cells in order to analyse their impacts on the synthesis process of cytochrome b558. According to the impact of these mutations on the level of NOX2 expression and activity, mutants were categorized in group A (W18C, E309K, K315del, I325F) characterized by a linear relationship between NOX2 expression and the NADPH ...
Source: BJ Disease - September 25, 2014 Category: Biochemistry Authors: S Beaumel, D Grunwald, F Fieschi, M Stasia Tags: BJ Biomolecules Source Type: research
Nucleotide binding triggers a conformational change of the CBS module of the magnesium transporter CNNM2 from a twisted towards a flat structure
Recent studies suggest cyclin M2 (CNNM2) to be part of the long-sought basolateral Mg2+ extruder at the renal distal convoluted tubule, or as its regulator. Here, we explore structural features and ligand binding capacities of the Bateman module of CNNM2 (residues 429-584), a domain involved in Mg2+ handling by the bacterial Mg2+ transporter MgtE, and AMP binding by the Mg2+ efflux protein CorC. Additionally, we studied the structural impact of the pathogenic mutation T568I, located in this region. Our crystal structures reveal that nucleotides bind at only one of the two cavities present in CNN...
Source: BJ Disease - September 3, 2014 Category: Biochemistry Authors: M Corral-Rodríguez, M Stuiver, G Abascal-Palacios, T Diercks, I Oyenarte, J Ereño-Orbea, A Ibáñez De Opakua, F J Blanco, J Encinar, V Spiwok, H Terashima, A Accardi, D Müller, L Alfonso Martinez-Cruz Tags: BJ Biomolecules Source Type: research
Ribosomal protein S19 binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism.
The hantaviral zoonotic diseases pose significant threat to human health due to the lack of potential antiviral therapeutics or a vaccine against hantaviruses. Sin Nombre hantavirus nucleocapsid protein (N) augments mRNA translation. N binds to both the mRNA 5’ cap and 40S ribosomal subunit via ribosomal protein S19 (RPS19). N with the assistance of viral mRNA 5’ untranslated region (UTR) preferentially favors the translation of downstream open reading frame. We identified and characterized the RPS19 binding domain at the N-terminus of N. Its deletion did not influence the secondary structure but impacted the...
Source: BJ Disease - July 25, 2014 Category: Biochemistry Authors: S S Ganaie, A Haque, E Cheng, T S Bonny, N N Salim, M A Mir Tags: BJ Disease Source Type: research
Prion-induced and spontaneous formation of transmissible toxicity in PrP transgenic Drosophila
Prion diseases are fatal transmissible neurodegenerative diseases of various mammalian species. Central to these conditions is the conversion of the normal host protein PrPC into the abnormal conformer PrPSc. Mature PrPC is attached to the plasma membrane by a glycosylphosphatidylinositol anchor, while during biosynthesis and metabolism cytosolic, and secreted forms of the protein may arise. The role of topological PrPC variants in the mechanism of prion formation and prion-induced neurotoxicity during prion disease remains undefined. Here we investigated whether Drosophila transgenic for ovine PrP targeted to the plasma m...
Source: BJ Disease - July 7, 2014 Category: Biochemistry Authors: A M Thackray, Y Di, C Zhang, H Wolf, L Pradl, I Vorberg, O Andréoletti, R Bujdoso Tags: BJ Disease Source Type: research
