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https://www.readbyqxmd.com/read/27922192/evidence-for-pipecolate-oxidase-in-mediating-protection-against-hydrogen-peroxide-stress
#1
Sathish Kumar Natarajan, Ezhumalai Muthukrishnan, Oleh Khalimonchuk, Justin L Mott, Donald F Becker
Pipecolate, an intermediate of the lysine catabolic pathway, is oxidized to Δ(1) -piperideine-6-carboxylate (P6C) by the flavoenzyme L-pipecolate oxidase (PIPOX). P6C spontaneously hydrolyzes to generate α-aminoadipate semialdehyde, which is then converted into α-aminoadipate acid by α-aminoadipatesemialdehyde dehydrogenase. L-pipecolate was previously reported to protect mammalian cells against oxidative stress. Here, we examined whether PIPOX is involved in the mechanism of pipecolate stress protection...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27922189/optimal-arac-cytotoxicity-to-aml-cells-requires-erk5-activity
#2
Ruifang Zheng, George P Studzinski
Cytarabine (AraC) has been the primary treatment agent for Acute Myeloid Leukemia (AML) in the past 30 years, but the precise mechanism of its action is not completely known. Here we assessed the role of ERK5 in AraC-induced cell death in AML cell lines HL60 and U937 using ERK5 inhibitors BIX02189 and XMD8-92. We report that inhibition of MEK5/ERK5 activity reduces AraC-induced cell death, DNA damage, the upregulated DNA damage biomarkers, and produced G2 phase cell cycle arrest. In addition, the pro-survival protein P-Bcl2 Ser70 was found to be associated with decreased AraC-induced cell death following XMD8-92 treatment, suggesting a regulatory role of ERK5 on Bcl2 phosphorylation...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27922110/%C3%AE-h2ax-53bp1-pkap-1-foci-and-their-linear-tracks-induced-by-in-vitro-exposure-to-radon-and-its-progeny-in-human-peripheral-blood-lymphocytes
#3
Defang Ding, Yaping Zhang, Jing Wang, Xufei Wang, Dunhuang Fan, Linfeng He, Xuxia Zhang, Yun Gao, Qiang Li, Honghong Chen
The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922109/regulation-of-hepcidin-expression-by-inflammation-induced-activin-b
#4
Yohei Kanamori, Makoto Sugiyama, Osamu Hashimoto, Masaru Murakami, Tohru Matsui, Masayuki Funaba
Activin B is induced in response to inflammation in the liver and enhances hepcidin expression, but the source of activin B and the molecular mechanism underlying hepcidin induction are not clear yet. Lipopolysaccharide (LPS)-induced inflammation induced inhibin βB but not inhibin α or inhibin βA expression in the liver, implicating activin B induction. Immunoreactive inhibin βB was detected in endothelial cells and Kupffer cells in LPS-treated liver. Activin B, but not activin A or activin AB, directly increased hepcidin expression...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922102/slc2a8-glut8-is-a-mammalian-trehalose-transporter-required-for-trehalose-induced-autophagy
#5
Allyson L Mayer, Cassandra B Higgins, Monique R Heitmeier, Thomas E Kraft, Xia Qian, Jan R Crowley, Krzysztof L Hyrc, Wandy L Beatty, Kevin E Yarasheski, Paul W Hruz, Brian J DeBosch
Trehalose is a disaccharide demonstrated to mitigate disease burden in multiple murine neurodegenerative models. We recently revealed that trehalose rapidly induces hepatic autophagy and abrogates hepatic steatosis by inhibiting hexose transport via the SLC2A family of facilitative transporters. Prior studies, however, postulate that intracellular trehalose is sufficient to induce cellular autophagy. The objective of the current study was to identify the means by which trehalose accesses the hepatocyte cytoplasm, and define the distal signaling mechanisms by which trehalose induces autophagy...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922075/cancer-associated-fibroblasts-treated-with-cisplatin-facilitates-chemoresistance-of-lung-adenocarcinoma-through-il-11-il-11r-stat3-signaling-pathway
#6
Leilei Tao, Guichun Huang, Rui Wang, Yan Pan, Zhenyue He, Xiaoyuan Chu, Haizhu Song, Longbang Chen
Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921261/attempting-to-compensate-for-reduced-neuronal-nitric-oxide-synthase-protein-with-nitrate-supplementation-cannot-overcome-metabolic-dysfunction-but-rather-has-detrimental-effects-in-dystrophin-deficient-mdx-muscle
#7
Cara A Timpani, Adam J Trewin, Vanesa Stojanovska, Ainsley Robinson, Craig A Goodman, Kulmira Nurgali, Andrew C Betik, Nigel Stepto, Alan Hayes, Glenn K McConell, Emma Rybalka
Duchenne muscular dystrophy arises from the loss of dystrophin and is characterized by calcium dysregulation, muscular atrophy, and metabolic dysfunction. The secondary reduction of neuronal nitric oxide synthase (nNOS) from the sarcolemma reduces NO production and bioavailability. As NO modulates glucose uptake, metabolism, and mitochondrial bioenergetics, we investigated whether an 8-week nitrate supplementation regimen could overcome metabolic dysfunction in the mdx mouse. Dystrophin-positive control (C57BL/10) and dystrophin-deficient mdx mice were supplemented with sodium nitrate (85 mg/l) in drinking water...
December 5, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27921184/chemotherapeutic-drug-selectivity-between-wild-type-and-mutant-braf-kinases-in-colon-cancer
#8
Jianchun Zhang, Tao Ji
Oncogenic BRaf V600E mutation is involved in the development, invasion and metastasis of colon cancer. Selective inhibition of BRaf(V600E) mutant has been recognized as a therapeutic strategy for the cancer. Here, we carried out atomistic molecular dynamics (MD) simulations to characterize the structural basis, energetic property, and dynamics behavior of conformational change in BRaf activation loop upon the mutation. It is found that V600E mutation destabilizes inactive DFG-out conformation of activation loop and promotes its conversion to the active DFG-in conformation, thus conferring constitutive activity for BRaf kinase...
January 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/27921108/a-novel-antioxidant-peptide-derived-from-wheat-germ-prevents-high-glucose-induced-oxidative-stress-in-vascular-smooth-muscle-cells-in-vitro
#9
Siyuan Chen, Dingbo Lin, Yulong Gao, Xiaozhou Cao, Xinchun Shen
The ingestion of whole wheat products is responsible for the prevention of a number of chronic diseases. The aim of this study is to characterize the molecular properties of a novel wheat germ-derived antioxidant peptide (AOP) in protection against high glucose-induced oxidative stress in vascular smooth muscle cells (VSMCs). AOP (amino acid sequence AREGETVVPG) was isolated from wheat germ albumin using dual-enzymatic hydrolysis/separation, followed by MS/MS. The in vitro IC50 value for Fe(2+) chelation was 0...
December 6, 2016: Food & Function
https://www.readbyqxmd.com/read/27921103/solanesol-induces-the-expression-of-heme-oxygenase-1-via-p38-and-akt-and-suppresses-the-production-of-proinflammatory-cytokines-in-raw264-7-cells
#10
Xiangyang Yao, Binyu Lu, Chaotian Lü, Qin Bai, Dazhong Yan, Yanli Wu, Zibing Hong, Hui Xu
The aim of the present study was to examine the anti-inflammatory effect of solanesol and to elucidate the underlying mechanisms. Heme oxygenase-1 (HO-1) plays an important role in cytoprotection against oxidative stress and inflammation. Solanesol induced HO-1 expression both at the level of mRNA and proteins, resulting in increased HO-1 activity. Solanesol treatment enhanced the level of the phosphorylated form, nuclear translocation, ARE-binding, and transcriptional activity of Nrf2. p38 and Akt contributed to ARE-driven HO-1 expression...
December 6, 2016: Food & Function
https://www.readbyqxmd.com/read/27920766/a-degu-p-and-degq-dependent-regulatory-pathway-for-the-k-state-in-bacillus-subtilis
#11
Mathieu Miras, David Dubnau
The K-state in the model bacterium Bacillus subtilis is associated with transformability (competence) as well as with growth arrest and tolerance for antibiotics. Entry into the K-state is determined by the stochastic activation of the transcription factor ComK and occurs in about ∼15% of the population in domesticated strains. Although the upstream mechanisms that regulate the K-state have been intensively studied and are well understood, it has remained unexplained why undomesticated isolates of B. subtilis are poorly transformable compared to their domesticated counterparts...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27920472/anti-inflammatory-effect-of-cannabinoid-agonist-win55-212-on-mouse-experimental-colitis-is-related-to-inhibition-of-p38mapk
#12
Ya-Jing Feng, Yong-Yu Li, Xu-Hong Lin, Kun Li, Ming-Hua Cao
AIM: To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS: We established the colitis model in C57BL/6 mice by replacing the animals' water supply with 4% dextran sulfate sodium (DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27920257/pkr-mediates-inflammatory-response-induced-by-hyperosmotic-stress
#13
Kenneth T Farabaugh, Mithu Majumder, Bo-Jhih Guan, Raul Jobava, Jing Wu, Dawid Krokowski, Xing-Huang Gao, Andrew Schuster, Michelle Longworth, Edward D Chan, Massimiliano Bianchi, Madhusudan Dey, Antonis E Koromilas, Parameswaran Ramakrishnan, Maria Hatzoglou
High extracellular osmolarity results in a switch from an adaptive to an inflammatory gene expression program. We show that hyperosmotic stress activates the protein kinase R (PKR) independently of its RNA binding domain. In turn, PKR stimulated nuclear accumulation of nuclear factor-κB (NF-κB) p65 species phosphorylated at serine-536, which was paralleled by the induction of a subset of inflammatory NF-κB p65- responsive genes including inducible nitric oxide synthase (iNOS), IL-6, and IL-1β. The PKR mediated-hyperinduction of iNOS decreased cell survival in mouse embryonic fibroblasts via mechanisms involving nitric oxide (NO) synthesis and post-translational modification of proteins...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27920254/casein-kinase-2-is-linked-to-stress-granule-dynamics-through-phosphorylation-of-the-stress-granule-nucleating-protein-g3bp1
#14
Lucas C Reineke, Wei-Chih Tsai, Antrix Jain, Jason T Kaelber, Sung Yun Jung, Richard E Lloyd
Stress granules are large macromolecular aggregates that contain translation initiation complexes and mRNAs. Stress granule formation coincides with translational repression, and stress granules actively signal to mediate cell fate decisions by a) signaling to the translation apparatus to maintain translational repression, b) mount various transcriptional responses including innate immunity, and c) to repress apoptosis. Previous work showed G3BP1 is phosphorylated at serine 149, which regulates G3BP1 oligomerization, stress granule assembly, and RNase activity intrinsic to G3BP1...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27920218/a-molecular-basis-for-the-presentation-of-phosphorylated-peptides-by-hla-b-antigens
#15
Adán Alpízar, Fabio Marino, Antonio Ramos-Fernández, Manuel Lombardía, Anita Jeko, Florencio Pazos, Alberto Paradela, César Santiago, Albert J R Heck, Miguel Marcilla
As aberrant protein phosphorylation is a hallmark of tumor cells, the display of tumor-specific phosphopeptides by Human Leukocyte Antigen (HLA) class I molecules can be exploited in the treatment of cancer by T-cell-based immunotherapy. Yet, the characterization and prediction of HLA-I phospholigands is challenging as the molecular determinants of the presentation of such post-translationally modified peptides are not fully understood. Here, we employed a peptidomic workflow to identify 256 unique phosphorylated ligands associated with HLA-B*40, -B*27, -B*39 or -B*07...
December 5, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27920204/studies-on-the-detection-expression-glycosylation-dimerization-and-ligand-binding-properties-of-mouse-siglec-e
#16
Shoib Siddiqui, Flavio Schwarz, Stevan Springer, Zahra Khedri, Hai Yu, Lingquan Deng, Andrea Verhagen, Yuko Naito-Matsui, Weiping Jiang, Daniel Kim, Jie Zhou, Beibei Ding, Xi Chen, Nissi Varki, Ajit Varki
CD33-related Siglecs are a family of proteins widely expressed on innate immune cells. Binding of sialylated glycans or other ligands triggers signals that inhibit or activate inflammation. Immunomodulation by Siglecs has been extensively studied, but relationships between structure and functions are poorly explored. Here we present new data relating the structure and function of Siglec-E, the major CD33-related Siglec expressed on mouse neutrophils, monocytes, macrophages, and dendritic cells. We generated nine new rat monoclonal antibodies specific to mouse Siglec-E, with no cross-reactivity to Siglec-F...
December 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27920203/a-highly-active-isoform-of-lentivirus-restriction-factor-samhd1-in-mouse
#17
Nicolin Bloch, Sabine Gläsker, Poojitha Sitaram, Henning Hofmann, Caitlin N Shepard, Megan L Schultz, Baek Kim, Nathaniel R Landau
The triphosphohydrolase SAMHD1 restricts HIV-1 replication in nondividing myeloid cells by depleting the dNTP pool, preventing reverse transcription. SAMHD1 is also reported to have ribonuclease activity that degrades the virus genomic RNA. Human SAMHD1 is regulated by phosphorylation of its carboxy-terminus at T592, which abrogates its antiviral function yet has only a small effect on its phosphohydrolase activity. In the mouse, SAMHD1 is expressed as two isoforms (ISF1 and ISF2) that differ at the carboxy-terminus due to alternative splicing of the last coding exon...
December 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27920157/two-serk-receptor-like-kinases-interact-with-the-receptor-like-kinase-ems1-in-anther-cell-fate-determination
#18
Zhiyong Li, Yao Wang, Jian Huang, Nagib Ahsan, Gabriel Biener, Joel Paprocki, Jay J Thelen, Valerica Raicu, Dazhong Zhao
Cell signaling pathways mediated by leucine-rich repeat receptor-like kinases (LRR-RLK) are essential for plant growth, development and defense. The EMS1 (EXCESS MICROSPOROCYTES1) LRR-RLK and its small protein ligand TPD1 (TAPETUM DETERMINANT1) play a fundamental role in somatic and reproductive cell differentiation during early anther development in Arabidopsis (Arabidopsis thaliana). However, it is unclear whether other cell surface molecules serve as co-regulators of EMS1. Here, we show that SERK1 (SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE1) and SERK2 LRR-RLKs act redundantly as co-regulatory and physical partners of EMS1...
December 5, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27920156/nf%C3%AE%C2%BAb-induced-periostin-activates-integrin-%C3%AE-3-signaling-to-promote-renal-injury-in-gn
#19
Niki Prakoura, Panagiotis Kavvadas, Raphaёl Kormann, Jean-Claude Dussaule, Christos E Chadjichristos, Christos Chatziantoniou
De novo expression in the kidney of periostin, a protein involved in odontogenesis and osteogenesis, has been suggested as a biomarker of renal disease. In this study, we investigated the mechanism(s) of induction and the role of periostin in renal disease. Using a combination of bioinformatics, reporter assay, and chromatin immunoprecipitation analyses, we found that NFκB and other proinflammatory transcription factors induce periostin expression in vitro and that binding of these factors on the periostin promoter is enriched in glomeruli during experimental GN...
December 5, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27920123/selective-enhancement-of-insulin-sensitivity-in-the-endothelium-in-vivo-reveals-a-novel-proatherosclerotic-signalling-loop
#20
Hema Viswambharan, Nadira Y Yuldasheva, Anshuman Sengupta, Helen Imrie, Matthew C Gage, Natalie J Haywood, Andrew M Walker, Anna Skromna, Natalia Makova, Stacey L Galloway, Pooja Shah, Piruthivi Sukumar, Karen E Porter, Peter J Grant, Ajay M Shah, Celio X Santos, Jing Li, David J Beech, Stephen Wheatcroft, Richard M Cubbon, Mark T Kearney
RATIONALE: In the endothelium, insulin stimulates endothelial nitric oxide synthase (eNOS) to generate the anti-atherosclerotic signalling radical NO. Insulin resistant type 2 diabetes is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. OBJECTIVE: To answer this question we generated a mouse with endothelial cell (EC)-specific over-expression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer...
December 5, 2016: Circulation Research
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