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https://www.readbyqxmd.com/read/28636814/arsenic-compromises-both-p97-and-proteasome-functions
#1
Joseph Tillotson, Christopher J Zerio, Bryan Harder, Andrew Ambrose, Kevin S Jung, MinJin Kang, Donna D Zhang, Eli Chapman
Exposure to arsenic is a worldwide problem that affects more than 200 million people. The underlying mechanisms of arsenic toxicity have been difficult to ascertain due to arsenic's pleotropic effects. A number of recent investigations have shown arsenic can compromise protein quality control through the ubiquitin proteasome system (UPS) or the endoplasmic reticulum associated protein degradation (ERAD) pathway. In this report, a link between arsenic and protein quality control is reported. Biochemical and cellular data demonstrate a misregulation of the ATPase cycle of the ATPase associated with various cellular activities (AAA+) chaperone, p97...
June 21, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28623546/targeting-sphingosine-1-phosphate-signaling-for-cancer-therapy
#2
REVIEW
Zuoquan Xie, Hong Liu, Meiyu Geng
Sphingosine-1-phosphate (S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival, cell proliferation, cell migration, angiogenesis and many other cellular processes. S1P either activates S1P receptors (S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1P signaling and its pathogenic roles in diseases as well as in developing modulators of S1P signaling, including S1P agonists, S1P antagonists and sphingosine kinase (SphK) inhibitors...
May 27, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28621569/down-regulation-of-slcyp1-in-the-phloem-reduces-auxin-response-and-photosynthetic-rate-in-tomato-solanum-lycopersicum-plants
#3
Ziv Spiegelman, Amit Shahar, Shmuel Wolf
The tomato dgt mutant, containing a single mutation in the Cyclophilin1 (SlCyp1) gene, is auxin insensitive and exhibits a pleotropic phenotype that includes lack of lateral roots, malformed xylem structure and reduced root-to-shoot ratio. Recently, we found that the SlCyp1 protein is phloem-mobile and traffic from shoot to root to induce lateral root formation. These processes are achieved through activation of auxin-mediated developmental programs. Inhibition of the trafficked SlCyp1 activity at the target site resulted in inhibition of the auxin response, supporting the hypothesis that this protein is indeed a mobile signal...
June 16, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28620279/interleukin-6-deficiency-attenuates-retinal-ganglion-cell-axonopathy-and-glaucoma-related-vision-loss
#4
Franklin D Echevarria, Cathryn R Formichella, Rebecca M Sappington
The pleotropic cytokine interleukin-6 (IL-6) is implicated in retinal ganglion cell (RGC) survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT) and IL-6 knock-out mice (B6;129S2-IL6(t)(m1kopf)/J; IL-6-/-) after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28559299/the-disulfide-bond-formation-pathway-is-essential-for-anaerobic-growth-of-escherichia-coli
#5
Brian M Meehan, Cristina Landeta, Dana Boyd, Jonathan Beckwith
Disulfide bonds are critical to the stability and function of many bacterial proteins. In the periplasm of Escherichia coli, intramolecular disulfide bond formation is catalyzed by the two-component Dsb system. Inactivation of the Dsb pathway has been shown to lead to a number of pleotropic effects, though cells remain viable under standard laboratory conditions. However, we show here that dsb strains of E. coli reversibly filament under aerobic conditions and fail to grow anaerobically unless a strong oxidant is provided in the growth medium...
May 30, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28497128/innovative-therapeutics-designer-natriuretic-peptides
#6
Laura M G Meems, John C Burnett
Endogenous natriuretic peptides serve as potent activators of particulate guanylyl cyclase receptors and the second messenger cGMP. Natriuretic peptides are essential in maintenance of volume homeostasis, and can be of myocardial, renal and endothelial origin. Advances in peptide engineering have permitted the ability to pursue highly innovative drug discovery strategies. This has resulted in designer natriuretic peptides that go beyond native peptides in efficacy, specificity, and resistance to enzymatic degradation...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28464262/a-tale-of-agriculturalists-and-hunter-gatherers-exploring-the-thrifty-genotype-hypothesis-in-native-south-americans
#7
Guillermo Reales, Diego L Rovaris, Vanessa C Jacovas, Tábita Hünemeier, José R Sandoval, Alcibiades Salazar-Granara, Darío A Demarchi, Eduardo Tarazona-Santos, Aline B Felkl, Michele A Serafini, Francisco M Salzano, Rafael Bisso-Machado, David Comas, Vanessa R Paixão-Côrtes, Maria Cátira Bortolini
OBJECTIVES: To determine genetic differences between agriculturalist and hunter-gatherer southern Native American populations for selected metabolism-related markers and to test whether Neel's thrifty genotype hypothesis (TGH) could explain the genetic patterns observed in these populations. MATERIALS AND METHODS: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36 rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701)...
May 2, 2017: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/28448568/inhibitory-effects-of-fenretinide-metabolites-n-4-methoxyphenyl-retinamide-mpr-and-4-oxo-n-4-hydroxyphenyl-retinamide-3-keto-hpr-on-fenretinide-molecular-targets-%C3%AE-carotene-oxygenase-1-stearoyl-coa-desaturase-1-and-dihydroceramide-%C3%AE-4-desaturase-1
#8
Eugenia Poliakov, William Samuel, Todd Duncan, Danielle B Gutierrez, Nathan L Mata, T Michael Redmond
The therapeutic capacity of fenretinide (N-[4-hydroxyphenyl] retinamide; 4-HPR) has been demonstrated for several conditions, including cancer, obesity, diabetes, and ocular disease. Yet, the mechanisms of action for its pleiotropic effects are still undefined. We hypothesized that investigation of two of the major physiological metabolites of fenretinide, N-[4-methoxyphenyl]retinamide (MPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (3-keto-HPR), might begin to resolve the multifaceted effects of this synthetic retinoid...
2017: PloS One
https://www.readbyqxmd.com/read/28445598/dabigatran-enhances-platelet-reactivity-and-platelet-thrombin-receptor-expression-in-patients-with-atrial-fibrillation-reply
#9
Alina Achilles, Annemarie Mohring, Tobias Zeus, Malte Kelm, Amin Polzin
Firstly, we would like to thank Bonello et al. for their comment on our recent publication. We completely agree that until now, data were contradicting regarding the impact of dabigatran on platelet reactivity. Additionally, we completely agree that during the last year, different groups have clearly shown enhanced platelet aggregation and platelet adhesion in dabigatran treated patients. [1-3] Furthermore, two different mechanisms have been described (enhanced platelet adhesion to the endothelium mediated by GPIb-α by Petzold et al...
April 26, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28426765/allatotropin-a-pleiotropic-neuropeptide-that-elicits-mosquito-immune-responses
#10
Salvador Hernández-Martínez, Minerva Sánchez-Zavaleta, Kevin Brito, Antonia Herrera-Ortiz, Sheila Ons, Fernando G Noriega
Allatotropins (AT) are neuropeptides with pleotropic functions on a variety of insect tissues. They affect processes such as juvenile hormone biosynthesis, cardiac rhythm, oviduct and hindgut contractions, nutrient absorption and circadian cycle. The present work provides experimental evidence that AT elicits immune responses in two important mosquito disease vectors, Anopheles albimanus and Aedes aegypti. Hemocytes and an immune-competent mosquito cell line responded to AT by showing strong morphological changes and increasing bacterial phagocytic activity...
2017: PloS One
https://www.readbyqxmd.com/read/28423621/epstein-barr-virus-encoded-microrna-bart7-regulates-radiation-sensitivity-of-nasopharyngeal-carcinoma
#11
Wei Gao, Zeng-Hong Li, Siqi Chen, Jimmy Yu-Wai Chan, Min Yin, Min-Juan Zhang, Thian-Sze Wong
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is very sensitive to radiotherapy. To date, the underlying mechanism remains poorly understood. Here, we demonstrated that expression of EBV-encoded microRNA BART7 (ebv-miR-BART7) increases responsiveness of NPC to radiation treatment by targeting GFPT1/TGFβ1 signaling. GFPT1 is the the key rate-limiting enzyme of the hexosamine signaling pathway and governs TGFβ1 production. TGFβ1, a pleotropic cytokine with the potency to trigger self-renewal and damage-repair machinery in somatic cells...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406646/transforming-sphingosine-kinase-1-inhibitors-into-dual-and-sphingosine-kinase-2-selective-inhibitors-design-synthesis-and-in-vivo-activity
#12
Elizabeth S Childress, Yugesh Kharel, Anne M Brown, David R Bevan, Kevin R Lynch, Webster L Santos
Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with its five G-protein coupled receptors (S1P1-5) to regulate cell growth and survival and has been implicated in a variety of diseases including cancer and sickle cell disease. As the key mediators in the synthesis of S1P, sphingosine kinase (SphK) isoforms 1 and 2 have attracted attention as viable targets for pharmaceutical inhibition. In this article, we describe the design, synthesis, and biological evaluation of aminothiazole-based guanidine inhibitors of SphK...
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28366515/coq10-selective-miscibility-and-penetration-into-lipid-monolayers-with-lower-lateral-packing-density
#13
Sumit Garg, Vandana Swaminathan, Sirisha Dhavala, Michael A Kiebish, Rangaprasad Sarangarajan, Niven R Narain
CoQ10 is ubiquitously present in eukaryotic cells. It acts as electron carrier in the electron transport chain of the inner membrane of the mitochondria to facilitate aerobic cellular respiration. A highly stable lipid nanodispersion formulation containing CoQ10 (BPM31510) is currently in clinical investigation for treatment of cancer. This study was designed to determine whether biophysical interactions between CoQ10 and lipid, in part, explain the observed stability and cellular accumulation of CoQ10 in cells and tissues...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28343015/systemic-delivery-of-the-tumor-necrosis-factor-gene-to-tumors-by-a-novel-dual-dna-nanocomplex-in-a-nanoparticle-system
#14
Vasundhara Shukla, Manu Dalela, Manika Vij, Ralph Weichselbaum, Surender Kharbanda, Munia Ganguli, Donald Kufe, Harpal Singh
Many cancers fail to respond to immunotherapy as a result of immune suppression by the tumor microenvironment. The exogenous expression of immune cytokines to reprogram the tumor microenvironment represents an approach to circumvent this suppression. The present studies describe the development of a novel dual nanoparticle (DNP) system for driving DNA expression vectors encoding inflammatory cytokines in tumor cells. The DNP system consists of a DNA expression vector-cationic peptide nanocomplex (NC) surrounded by a diblock polymeric NP...
March 23, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28320879/metabolism-shapes-the-cell
#15
REVIEW
Anthony M Sperber, Jennifer K Herman
More than 5 decades of work support the idea that cell envelope synthesis, including the inward growth of cell division, is tightly coordinated with DNA replication and protein synthesis through central metabolism. Remarkably, no unifying model exists to account for how these fundamentally disparate processes are functionally coupled. Recent studies demonstrate that proteins involved in carbohydrate and nitrogen metabolism can moonlight as direct regulators of cell division, coordinate cell division and DNA replication, and even suppress defects in DNA replication...
June 1, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28294872/-pleotropic-effects-of-atorvastatin-in-patients-with-chronic-ischemic-heart-disease
#16
V P Mikhin, Yu A Zhilyaeva, N I Gromnaky
Examined 52 patients with a diagnosis Ischemic heart disease: stable angina II-III FC CHF I-IIA stage, in combination with hypercholesterolemia aged 53-65 years (58,2+/-6,5), receiving together with traditional antianginal therapy generic atorvastatin Torvakard in the dose of 10 mg/day (20 people) with the level of total cholesterol from 5.0 to 6.50 mmol/l, patients with cholesterol levels from is 6.51 to 8.0 mmol/l was taking Torvakard 20 mg/day (32 person). As a result of 3 months therapy with low doses of Torvakarda decreased level of CRP, endothelin-1, IMT, improving the parameters of endothelium-dependent vasodilation, which shows the positive impact of the drug on morphological and functional parameters of the vascular wall...
May 2016: Kardiologiia
https://www.readbyqxmd.com/read/28256636/elevated-fibroblast-growth-factor-21-fgf21-in-obese-insulin-resistant-states-is-normalised-by-the-synthetic-retinoid-fenretinide-in-mice
#17
Nicola Morrice, George D Mcilroy, Seshu R Tammireddy, Jennifer Reekie, Kirsty D Shearer, Mary K Doherty, Mirela Delibegović, Phillip D Whitfield, Nimesh Mody
Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinide inhibits obesity and improves glucose homeostasis in mice and has pleotropic effects on cellular pathways. To identify Fenretinide target genes, we performed unbiased RNA-seq analysis in liver from mice fed high-fat diet ± Fenretinide. Strikingly, Fgf21 was the most downregulated hepatic gene...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28239611/pleotropic-acute-and-chronic-effects-of-leptin-to-reverse-type-1-diabetes
#18
Rachel J Perry
Recent studies have demonstrated that leptin can prolong life chronically in rats with poorly-controlled type 1 diabetes (T1D). Multiple explanations have been proposed to explain leptin's chronic antihyperglycemic effect, including suppression of glucagon release and/or signaling, reductions in hyperphagia and ectopic lipid content, and improvements in insulin sensitivity; it is leptin's ability to reduce plasma glucose relies on all of these effects. In addition, leptin reverses hyperglycemia and diabetic ketoacidosis (DKA) acutely, within 6 hours of leptin infusion, by suppressing hypothalamic-pituitary-adrenal (HPA) axis activity in insulinopenic rats...
January 2017: Postdoc Journal
https://www.readbyqxmd.com/read/28166722/integration-of-vdr-genome-wide-binding-and-gwas-genetic-variation-data-reveals-co-occurrence-of-vdr-and-nf-%C3%AE%C2%BAb-binding-that-is-linked-to-immune-phenotypes
#19
Prashant K Singh, Patrick R van den Berg, Mark D Long, Angie Vreugdenhil, Laurie Grieshober, Heather M Ochs-Balcom, Jianmin Wang, Sylvie Delcambre, Sami Heikkinen, Carsten Carlberg, Moray J Campbell, Lara E Sucheston-Campbell
BACKGROUND: The nuclear hormone receptor superfamily acts as a genomic sensor of diverse signals. Their actions are often intertwined with other transcription factors. Nuclear hormone receptors are targets for many therapeutic drugs, and include the vitamin D receptor (VDR). VDR signaling is pleotropic, being implicated in calcaemic function, antibacterial actions, growth control, immunomodulation and anti-cancer actions. Specifically, we hypothesized that the biologically significant relationships between the VDR transcriptome and phenotype-associated biology could be discovered by integrating the known VDR transcription factor binding sites and all published trait- and disease-associated SNPs...
February 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28164169/adeno-associated-virus-serotype-9-driven-expression-of-bag3-improves-left-ventricular-function-in-murine-hearts-with-left-ventricular-dysfunction-secondary-to-a-myocardial-infarction
#20
Tijana Knezevic, Valerie D Myers, Feifei Su, JuFang Wang, Jianliang Song, Xue-Qian Zhang, Erhe Gao, Guofeng Gao, Madesh Muniswamy, Manish K Gupta, Jennifer Gordon, Kristen N Weiner, Joseph Rabinowitz, Frederick V Ramsey, Douglas G Tilley, Kamel Khalili, Joseph Y Cheung, Arthur M Feldman
OBJECTIVES: The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BACKGROUND: BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure...
December 2016: JACC. Basic to Translational Science
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