cAMP ameliorates inflammation in macrophages by modulation of receptor for advanced glycation end-products
This study should deepen our understanding of the pathogenesis of RAGE-mediated tissue derangement and provide new clues for overcoming RAGE-related inflammatory diseases. (Source: BJ Disease)
Source: BJ Disease - July 4, 2014 Category: Biochemistry Authors: S Motoyoshi, Y Yamamoto, S Munesue, H Igawa, A Harashima, H Saito, D Han, T Watanabe, H Sato, H Yamamoto Tags: BJ Disease Source Type: research
Amyloid {beta} peptide-dependent activation of human platelets: essential role of Ca2{+} and ADP in aggregation and thrombus formation
In this study, we investigated the effect of Aβ peptides on human platelet signal transduction and function. We discovered that the 25-35 domain of Aβ peptides induce an increase in platelet intracellular Ca2+ that stimulates α- and dense granule secretion and leads to the release of the secondary agonist ADP. Released ADP acts in an autocrine manner as a stimulant for critical signaling pathways leading to the activation of platelets. This includes the activation of the protein kinases Syk, protein kinase C, Akt, and mitogen-activated protein kinases. Ca2+-dependent release of ADP is als...
Source: BJ Disease - July 1, 2014 Category: Biochemistry Authors: I Canobbio, G Francesco Guidetti, B Oliviero, D Manganaro, D Vara, M Torti, G Pula Tags: BJ Signal Source Type: research
DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis
Parkinson’s Disease (PD) is a complex disorder that is associated with neuronal loss or dysfunction caused by genetic risks, environmental factors and advanced aging. It has been reported that DJ-1 mutations rendered neurons sensitive to oxidative damage, which led to the onset of familiar PD. However, the molecular mechanism is still unclear. Here we show that DJ-1 interacts with RACK1 (receptor of activated C kinase 1) and increases its dimerization and protein stability. The DJ-1 transgene protects cortical neurons from H2O2 induced apoptosis, and this protective effect is abrogated by knocking down RACK1. Simila...
Source: BJ Disease - June 20, 2014 Category: Biochemistry Authors: J Ma, R Wu, Q Zhang, J Wu, J Lou, Z Zheng, J Ding, Z Yuan Tags: BJ Signal Source Type: research
The neurotoxicity of 5-S-cysteinyldopamine is mediated by the early activation of ERK1/2 followed by the subsequent activation of ASK-1/JNK1/2 pro-apoptotic signalling
Parkinson’s disease is characterized by the progressive and selective loss of dopaminergic neurons in the substantia nigra. It has been postulated that endogenously formed 5-S-cysteinyldopamine (CysDA) and its metabolites may be, in part, responsible for this selective neuronal loss, although the mechanisms by which they contribute to such neurotoxicity are not understood. Exposure of neurons in culture to CysDA caused cell injury, apparent 12-48 h post-exposure. A portion of the neuronal death induced by CysDA was preceded by a rapid uptake and intracellular oxidation of CysDA, leading to an acute and transient act...
Source: BJ Disease - June 18, 2014 Category: Biochemistry Authors: D Vauzour, J T. Pinto, A J. L. Cooper, J P.E. Spencer Tags: BJ Disease Source Type: research
Key elements of the RNA interference pathway are regulated by Hepatitis B virus replication and HBx acts as a viral suppressor of RNA silencing
The host-mediated RNA interference pathways (RNAi) restrict replication of viruses in plant, invertebrate and vertebrate systems. However, comparatively little is known about the interplay between RNAi and various viral infections in mammalian hosts. We show here that the siRNA mediated silencing of Drosha, Dicer and Ago2 transcripts in Huh7 cells resulted in elevated levels of HBV specific RNAs, and conversely, we observed a decrease in mRNA and protein levels of same RNAi components in HepG2 cells infected with HBV. Similar reductions were also detectable in chronic hepatitis B (CHB) patients. Analysis of CHB liver biops...
Source: BJ Disease - June 6, 2014 Category: Biochemistry Authors: M Chinnappan, A Kumar Singh, P Kakumani, G Kumar, S Babasaheb Rooge, A Kumari, A Varshney, A Rastogi, A Kumar Singh, S Kumar Sarin, P Malhotra, S Kumar Mukherjee, R Kamal Bhatnagar Tags: BJ Disease Source Type: research
A Unique, Phosphorylation Dependent, eIF4E Assembly on 40S Ribosomes Coordinated by Hepatitis C Virus Protein NS5A that Activates Internal Ribosome Entry Site Translation
In this report, we demonstrate that NS5A coordinates a unique assembly of cap binding protein eIF4E and 40S ribosome to form a complex that we call ENR (eIF4E-NS5A-Ribosome). Recruitment of NS5A and eIF4E to 40S ribosome was confirmed by polysome fractionation, sub-cellular fractionation and high salt wash immunoprecipitation. These observations were confirmed in HCV infected cells as well, validating its biological significance. eIF4E phosphorylation was critical for ENR assembly. 80S ribosome dissociation and RNase integrity assays revealed that once associated, ENR complex is stable and RNA interaction is dispensable. B...
Source: BJ Disease - June 4, 2014 Category: Biochemistry Authors: S Panda, D Vedagiri, T Soundara Viveka, K Harinivas Harshan Tags: BJ Gene Source Type: research
Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity
In Alzheimer disease, the microtubule-associated protein tau dissociates from the neuronal cytoskeleton and aggregates to form cytoplasmic inclusions. Although hyper-phosphorylation of tau Ser and Thr residues is an established trigger of tau misfunction and aggregation, tau modifications extend to Lys residues as well, raising the possibility that different modification signatures depress or promote aggregation propensity depending on site occupancy. To identify Lys-residue modifications associated with normal tau function, soluble tau proteins isolated from four cognitively normal human brains were characterized by mass ...
Source: BJ Disease - May 28, 2014 Category: Biochemistry Authors: K E Funk, S N Thomas, K N Schafer, G L Cooper, Z Liao, D J Clark, A J Yang, J Kuret Tags: BJ Disease Source Type: research
Impaired selenoprotein expression in brain triggers striatal neuronal loss leading to coordination defects in mice
Selenocysteine Insertion Sequence (SECIS)-Binding Protein 2 (Secisbp2) binds to SECIS elements located in the 3’-untranslated region of eukaryotic selenoprotein mRNAs. It facilitates incorporation of the rare amino acid selenocysteine in response to UGA codons. Inactivation of Secisbp2 in hepatocytes greatly reduced selenoprotein levels. Neuron-specific inactivation of Secisbp2 (CamK-Cre; Secisbp2fl/fl) reduced cerebral expression of selenoproteins to a lesser extent than inactivation of tRNA[Ser]Sec. This allowed us to study the development of cortical parvalbumin-positive (PV+) interneurons, which are compl...
Source: BJ Disease - May 20, 2014 Category: Biochemistry Authors: S Seeher, B A Carlson, A C Miniard, E K Wirth, Y Mahdi, D L Hatfield, D M Driscoll, U Schweizer Tags: BJ Disease Source Type: research
HEXIM1 Plays a Critical Role in the Inhibition of the Androgen Receptor by Antiandrogens
We show that Hexamethylene-bis-acetamide-inducible protein 1(HEXIM1) functions as an androgen receptor (AR) co-repressor as it physically interacts with the AR and is required for the ability of antiandrogens to inhibit androgen-induced target gene expression and cell proliferation. OncomineTM database and IHC analyses of human prostate tissues revealed that expression of HEXIM1 mRNA and protein are down-regulated during the development and progression of prostate cancer. Enforced downregulation of HEXIM1 in parental hormone-dependent LNCaP cells results in resistance to the inhibitory action of antiandrogens. Conversely, ...
Source: BJ Disease - May 20, 2014 Category: Biochemistry Authors: I Yeh, K Song, B M Wittmann, X Bai, D Danielpour, M M Montano Tags: BJ Gene Source Type: research
Characterisation of human variants in obesity-related SIM1 protein identifies a hotspot for dimerisation with the partner protein ARNT2
In this study we assess a number of human SIM1 variants with reduced activity and determine that frequently, impaired function is due to defects in dimerisation with essential partner protein aryl hydrocarbon nuclear translocator 2 (ARNT2). Equivalent variants generated in highly-related protein Single-minded 2 (SIM2) produce near-identical impaired function and dimerisation defects, indicating that these effects are not unique to the structure of SIM1. Based on this data, we predict that other select human SIM1 and SIM2 variants reported in human genomic databases will also be deficient in activity, and identify two new l...
Source: BJ Disease - May 12, 2014 Category: Biochemistry Authors: A E. Sullivan, A Raimondo, T A. Schwab, J B. Bruning, P Froguel, I Sadaf Farooqi, D J. Peet, M L. Whitelaw Tags: BJ Disease Source Type: research
Hypoxia Inducible Regulation of Placental BOK Expression
In this study, we identified a hypoxia-response element (HRE) at the junction of exon-1 and intron-1 (+229 to +279) in the human BOK gene as well as an antisense transcript driven by a promoter located in intron-2. The isolated BOK-HRE bound hypoxia-inducible HIF proteins in vitro as well as in trophoblastic JEG3 cells and was functional in its natural position as well as in front of a heterologous promoter. Being a reverted repeat, the BOK-HRE functioned in both orientations. This directionless feature of the BOK-HRE facilitates hypoxia regulation via HIF of both BOK and its antisense transcript as demonstra...
Source: BJ Disease - May 8, 2014 Category: Biochemistry Authors: D Luo, I Caniggia, M Post Tags: BJ Disease Source Type: research
Mouse model for deficiency of methionine synthase reductase exhibits short-term memory impairment and disturbances in brain choline metabolism
Hyperhomocysteinemia can contribute to cognitive impairment and brain atrophy. Methionine synthase reductase (MTRR) activates methionine synthase, which catalyzes homocysteine remethylation to methionine. Severe MTRR deficiency results in homocystinuria with cognitive and motor impairments. An MTRR polymorphism may influence homocysteine levels and reproductive outcomes. The goal of this study was to determine whether mild hyperhomocysteinemia impacts neurologic function in a mouse model with Mtrr deficiency. Three-month-old Mtrr+/+, Mtrr+/gt and Mtrrgt/gt mice were assessed for short-term memory, brai...
Source: BJ Disease - May 6, 2014 Category: Biochemistry Authors: N M Jadavji, R H Bahous, L Deng, O Malysheva, M Grand'Maison, B J Bedell, M A Caudill, R Rozen Tags: BJ Disease Source Type: research
A{beta} dimers differ from monomers in structural propensity, aggregation paths, and population of synaptotoxic assemblies
Dimers of the amyloid β-protein (Aβ) are believed to play an important role in Alzheimer’s disease. In the absence of sufficient brain-derived dimer we studied one of the only possible dimers that could be produced in vivo, dityrosine cross-linked Aβ, [Aβ]DiY. For comparison we used Aβ monomer and a design dimer cross-linked by substitution of serine 26 with cystine, [AβS26C]2. We show that like monomer, unaggregated dimers, lack appreciable structure and fail to alter LTP. Importantly, dimers exhibit subtly different structural propensities from monomer and each other, and ...
Source: BJ Disease - May 1, 2014 Category: Biochemistry Authors: T T. O'Malley, N Alia Oktaviani, D Zhang, A Lomakin, B O'Nuallain, S Linse, G B. Benedek, M J. Rowan, F A.A. Mulder, D M. Walsh Tags: BJ Biomolecules Source Type: research
The Cardiac Ryanodine Receptor Luminal Ca2{+} Sensor Governs Ca2{+} Waves, Ventricular Tachyarrhythmias, and Cardiac Hypertrophy in Calsequestrin Null Mice
Cardiac calsequestrin (CASQ2) is commonly believed to serve as the sarcoplasmic reticulum (SR) luminal Ca2+ sensor. Ablation of CASQ2 promotes spontaneous Ca2+ waves (SCWs) and catecholaminergic polymorphic ventricular tachycardia (CPVT) upon stress but not at rest. How SCWs and CPVT are triggered by stress in the absence of the CASQ2-based luminal Ca2+ sensor is an important unresolved question. Here we assessed the role of the newly identified RyR2-resident luminal Ca2+ sensor in determining SCW propensity, CPVT susceptibility, and cardiac hypertrophy in Casq2 knockout (KO) mice. We crossbred ...
Source: BJ Disease - April 23, 2014 Category: Biochemistry Authors: J Zhang, B Chen, X Zhong, T Mi, A Guo, Q Zhou, Z Tan, G Wu, A W Chen, M Fill, L Song, S Chen Tags: BJ Biomolecules Source Type: research
Ceramide Synthase 4 deficiency in mice causes lipid alterations in sebum and results in alopecia
Five ceramide synthases (CerS2‑6) are expressed in mouse skin. While CerS3 has been shown to fulfill an essential function during skin development, neither CerS6 nor CerS2 deficient mice show an obvious skin phenotype. In order to study the role of CerS4, we generated CerS4 deficient mice (CerS4-/-) and CerS4 specific antibodies. With these biological tools we analyzed the tissue distribution and determined the cell type specific expression of CerS4 in suprabasal epidermal layers of footpads as well as in sebaceous glands of the dorsal skin. Loss of CerS4 protein leads to an altered lipid composition of the sebum, w...
Source: BJ Disease - April 17, 2014 Category: Biochemistry Authors: P Ebel, S Imgrund, K vom Dorp, K Hofmann, H Maier, H Drake, J Degen, P Dörmann, M Eckhardt, T Franz, K Willecke Tags: BJ Gene Source Type: research
