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https://www.readbyqxmd.com/read/28642969/diverse-metabolic-effects-of-o-glcnacylation-in-the-pancreas-but-limited-effects-in-insulin-sensitive-organs-in-mice
#1
Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
AIMS/HYPOTHESIS: O-GlcNAcylation is characterised by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) and serves in sensing intracellular nutrients by modulating various cellular processes. Although it has been speculated that O-GlcNAcylation is associated with glucose metabolism, its exact role in whole body glucose metabolism has not been fully elucidated. Here, we investigated whether loss of O-GlcNAcylation globally and in specific organs affected glucose metabolism in mammals under physiological conditions...
June 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28642958/phosphorylation-of-a-full-length-amyloid-%C3%AE-peptide-modulates-its-amyloid-aggregation-cell-binding-and-neurotoxic-properties
#2
Elaheh Jamasbi, Frances Separovic, Mohammed Akhter Hossain, Giuseppe Donato Ciccotosto
Amyloid beta peptide (Aβ) is the major protein component of the amyloid plaques that are present in the brains of Alzheimer's disease (AD) patients. Aβ42 peptide is a known neurotoxic agent that binds to neurons and, under specific aggregation conditions, triggers cell death. Aβ peptide can undergo specific amino acid posttranslational modifications, such as phosphorylation, that are important for modulating its proteolytic degradation, aggregation, binding to lipid membranes and neurotoxic functions. Peptides phosphorylated at serine 8 in full-length Aβ42 (pAβ42) were synthesised and compared to native Aβ42 peptide...
June 23, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28641522/advances-on-ppar%C3%AE-research-in-the-emerging-era-of-precision-medicine
#3
Pinyi Lu, Zhongming Zhao
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily that functions as a ligand-inducible transcription factor. It regulates glucose and lipid metabolism, immunity, and cellular growth and differentiation. Thiazolidinediones (TZDs) are potent insulin sensitizers that function by activating PPARs, with a high specificity for PPARγ. Due to their ability to preserve pancreatic beta cell function and reduce insulin resistance, TZDs have become one of the most prescribed classes of medications for type 2 diabetes (T2D) since their approval by the US Food and Drug Administration (FDA) and initial use in 1997...
June 21, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28640877/identification-of-c-ebp%C3%AE-as-a-novel-target-of-the-hpv8-e6-protein-regulating-mir-203-in-human-keratinocytes
#4
Anna M Marthaler, Marta Podgorska, Pascal Feld, Alina Fingerle, Katrin Knerr-Rupp, Friedrich Grässer, Hans Smola, Klaus Roemer, Elke Ebert, Yoo-Jin Kim, Rainer M Bohle, Cornelia S L Müller, Jörg Reichrath, Thomas Vogt, Magdalena Malejczyk, Sławomir Majewski, Sigrun Smola
Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28638997/follistatin-treatment-suppresses-serca1b-levels-independently-of-other-players-of-calcium-homeostasis-in-c2c12-myotubes
#5
János Fodor, Adrienn Gomba-Tóth, Tamás Oláh, János Almássy, Ernő Zádor, László Csernoch
Follistatin (FS) is a high affinity activin-binding protein, neutralizing the effects of the Transforming Growth Factor-beta (TGF-β) superfamily members, as myostatin (MSTN). Since MSTN emerged as a negative regulator, FS has been considered as a stimulator of skeletal muscle growth and differentiation. Here, we studied the effect of FS administration on the Ca(2+)-homeostasis of differentiating C2C12 skeletal muscle cells. FS-treatment increased the fusion index, the size of terminally differentiated myotubes, and transiently elevated the expression of the calcium-dependent protein phosphatase, calcineurin, at the beginning of differentiation...
June 21, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28637867/full-length-cellular-beta-secretase-has-a-trimeric-subunit-stoichiometry-and-its-sulfur-rich-transmembrane-interaction-site-modulates-cytosolic-copper-compartmentalization
#6
Filip Liebsch, Mark R P Aurousseau, Tobias Bethge, Hugo McGuire, Silvia Scolari, Andreas Herrmann, Rikard Blunck, Derek Bowie, Gerd Multhaup
The beta-secretase (BACE1) initiates processing of the amyloid precursor protein (APP) into Aβ peptides, which have been implicated as central players in the pathology of Alzheimer disease. BACE1 has been described as a copper-binding protein and its oligomeric state as being monomeric, dimeric, and/or multimeric, but the native cellular stoichiometry has remained elusive. Here, by using single-molecule fluorescence and in vitro cross-linking experiments with photo-activatable unnatural amino acids, we show that full-length BACE1, independently of its subcellular localization, exists as trimers in human cells...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28637452/downregulation-of-talin-1-expression-associates-with-increased-proliferation-and-migration-of-vascular-smooth-muscle-cells-in-aortic-dissection
#7
Xiaolong Wei, Yudong Sun, Yani Wu, Jiang Zhu, Bin Gao, Han Yan, Zhiqing Zhao, Jian Zhou, Zaiping Jing
BACKGROUND: This study aimed to assessed whether Talin-1 is involved in the pathogenesis of aortic dissection via regulating vascular smooth muscle cell (VSMC) biological function. METHODS: Human aortic samples were obtained from organ donors who died from nonvascular diseases as normal controls and from patients undergoing surgical repair of thoracic aortic dissection. The expression level and distribution of Talin-1 were detected using westernblot analysis and immunohistochemistry in each sample...
June 20, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28634592/euglycemic-diabetic-ketoacidosis-with-prolonged-glucosuria-associated-with-the-sodium-glucose-cotransporter-2-canagliflozin
#8
Daniel A Kelmenson, Kelsey Burr, Yusra Azhar, Paul Reynolds, Chelsea A Baker, Neda Rasouli
Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control by a reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. This unique mechanism, independent of insulin secretion and beta cell function, has made this class of medication desirable in patients with type 2 diabetes. However in May 2015, the US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors...
April 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28634454/the-structure-and-function-of-the-na-k-atpase-isoforms-in-health-and-disease
#9
REVIEW
Michael V Clausen, Florian Hilbers, Hanne Poulsen
The sodium and potassium gradients across the plasma membrane are used by animal cells for numerous processes, and the range of demands requires that the responsible ion pump, the Na,K-ATPase, can be fine-tuned to the different cellular needs. Therefore, several isoforms are expressed of each of the three subunits that make a Na,K-ATPase, the alpha, beta and FXYD subunits. This review summarizes the various roles and expression patterns of the Na,K-ATPase subunit isoforms and maps the sequence variations to compare the differences structurally...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28630423/thymosin-beta-4-regulates-activation-of-hepatic-stellate-cells-via-hedgehog-signaling
#10
Jieun Kim, Jeongeun Hyun, Sihyung Wang, Chanbin Lee, Jae-Wook Lee, Eun-Yi Moon, Heejae Cha, Anna Mae Diehl, Youngmi Jung
The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA-treated LX-2. TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629856/ethnic-differences-in-glucose-effectiveness-and-disposition-index-in-overweight-obese-african-american-and-white-women-with-prediabetes-a-study-of-compensatory-mechanisms
#11
Kwame Osei, Trudy Gaillard
OBJECTIVE: Prediabetes, a major precursor of type 2 diabetes, varies among ethnic populations. Therefore, we compared the pathophysiologic mechanisms of prediabetes in overweight/obese African American (AA) and White American (WA) women. SUBJECTS AND METHODS: We recruited 95 women (67 AA, 28 WA) with prediabetes. Standard OGTT and FSIVGTT were performed in each subject. Insulin sensitivity (Si), glucose effectiveness (Sg), beta cell function (acute insulin response to glucose (AIRg) and disposition index (DI: Si×AIRg) were calculated using Bergman's Minmod...
March 14, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28628102/regulation-of-body-weight-and-energy-homeostasis-by-neuronal-cell-adhesion-molecule-1
#12
Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun-Xia Yi, Sonja C Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise van der Weyden, Andreas L Birkenfeld, Thoralf Niendorf, James F A Poulet, Tamas L Horvath, Matthias H Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N Poy
Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28626572/optical-control-of-a-receptor-linked-guanylyl-cyclase-using-a-photoswitchable-peptidic-hormone
#13
Tom Podewin, Johannes Broichhagen, Christina Frost, Dieter Groneberg, Julia Ast, Helena Meyer-Berg, Nicholas H F Fine, Andreas Friebe, Martin Zacharias, David J Hodson, Dirk Trauner, Anja Hoffmann-Röder
The optical control over biological function with small photoswitchable molecules has gathered significant attention in the last decade. Herein, we describe the design and synthesis of a small library of photoswitchable peptidomimetics based upon human atrial natriuretic peptide (ANP), in which the photochromic amino acid [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP) is incorporated into the peptide backbone. The endogeneous hormone ANP signals via the natriuretic peptide receptor A (NPR-A) through raising intracellular cGMP concentrations, and is involved in blood pressure regulation and sodium homeostasis, as well as lipid metabolism and pancreatic function...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28625845/injury-and-defective-regeneration-of-the-epithelial-basement-membrane-in-corneal-fibrosis-a-paradigm-for-fibrosis-in-other-organs
#14
REVIEW
Steven E Wilson, Gustavo K Marino, Andre A M Torricelli, Carla S Medeiros
Myofibroblast-mediated fibrosis is important in the pathophysiology of diseases in most organs. The cornea, the transparent anterior wall of the eye that functions to focus light on the retina, is commonly affected by fibrosis and provides an optimal model due to its simplicity and accessibility. Severe injuries to the cornea, including infection, surgery, and trauma, may trigger the development of myofibroblasts and fibrosis in the normally transparent connective tissue stroma. Ultrastructural studies have demonstrated that defective epithelial basement membrane (EBM) regeneration after injury underlies the development of myofibroblasts from both bone marrow- and keratocyte-derived precursor cells in the cornea...
June 15, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28625491/insulinotropic-action-of-2-4-dinitroanilino-benzoic-acid-through-the-attenuation-of-pancreatic-beta-cell-lesions-in-diabetic-rats
#15
Humera Jahan, M Iqbal Choudhary, Mehwish Manzoor, Khalid Mohammad Khan, Shahnaz Perveen, Atta-Ur Rahman
Beta cell destruction plays a key role in the pathogenesis of type 1 diabetes mellitus. It has also been argued that beta cell mass may also be compromised in some cases of type 2 diabetes, although this is controversial. Currently, the failure of oral antidiabetic insulin secretagogue drugs to properly correct type 2 diabetes demands novel approaches in the treatment of this condition. For any condition associated with diminished beta cell function, the aim of the present study was to investigate the in vitro and in vivo antidiabetic effect in STZ-induced diabetic rats, and maximum tolerated dose (MTD) safety of novel anthranilic acid derivative, 2, 4-dinitroanilino-benzoic acid (1)...
June 15, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28624356/vascular-ageing-underlying-mechanisms-and-clinical-implications
#16
REVIEW
Ageliki Laina, Konstantinos Stellos, Kimon Stamatelopoulos
Epidemiological studies have shown that ageing is a major non-reversible risk factor for cardiovascular disease. Vascular ageing starts early in life and is characterized by a gradual change of vascular structure and function resulting in increased arterial stiffening. At the present review we discuss the role of the most important molecular pathways involved in vascular ageing, their association with arterial stiffening and possible novel therapeutic targets that may delay this otherwise irreversible degenerating process...
June 14, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28623645/psmb5-is-associated-with-proliferation-and-drug-resistance-in-triple-negative-breast-cancer
#17
Wensong Wei, Yufeng Zou, Qihua Jiang, Zhibin Zhou, Haolong Ding, Liping Yan, Shixin Yang
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can't benefit fully from currently available targeted therapies. METHODS: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development...
June 15, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28622331/in-silico-assessment-of-genetic-variation-in-kcna5-reveals-multiple-mechanisms-of-human-atrial-arrhythmogenesis
#18
Michael A Colman, Haibo Ni, Bo Liang, Nicole Schmitt, Henggui Zhang
A recent experimental study investigating patients with lone atrial fibrillation identified six novel mutations in the KCNA5 gene. The mutants exhibited both gain- and loss-of-function of the atrial specific ultra-rapid delayed rectifier K+ current, IKur. The aim of this study is to elucidate and quantify the functional impact of these KCNA5 mutations on atrial electrical activity. A multi-scale model of the human atria was updated to incorporate detailed experimental data on IKur from both wild-type and mutants...
June 16, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28621586/the-cooler-code-a-novel-analytical-approach-to-calculate-subcellular-energy-deposition-by-internal-electron-emitters
#19
Mattia Siragusa, Giorgio Baiocco, Pil M Fredericia, Werner Friedland, Torsten Groesser, Andrea Ottolenghi, Mikael Jensen
COmputation of Local Electron Release (COOLER), a software program designed for dosimetry assessment at the cellular/subcellular scale, with a given distribution of administered low-energy electron-emitting radionuclides in cellular compartments, which remains a critical step in risk/benefit analysis for advancements in internal radiotherapy. The software is intended to overcome the main limitations of the medical internal radiation dose (MIRD) formalism for calculations of cellular S-values (i.e., dose to a target region in the cell per decay in a given source region), namely, the use of the continuous slowing down approximation (CSDA) and the assumption of a spherical cell geometry...
June 16, 2017: Radiation Research
https://www.readbyqxmd.com/read/28621263/loss-of-barx1-promotes-hepatocellular-carcinoma-metastasis-through-up-regulating-mgat5-and-mmp9-expression-and-indicates-poor-prognosis
#20
Guodong Wang, Jian Liu, Yi Cai, Jie Chen, Wenbing Xie, Xiangqian Kong, Wenjie Huang, Hao Guo, Xiaodi Zhao, Yuanyuan Lu, Lu Niu, Xiaowei Li, Haijia Zhang, Chao Lei, Zhijie Lei, Jipeng Yin, Hao Hu, Fan Yu, Yongzhan Nie, Limin Xia, Kaichun Wu
Metastasis is the major dominant reason for poor prognosis of hepatocellular carcinoma (HCC) after surgical treatment. However, the molecular mechanism of metastasis has not been well characterzied. Here, we report a novel function of Barx homeobox1 (Barx1) in inhibiting HCC invasion and metastasis. Barx1 expression is significantly decreased in human HCC tissues than in adjacent non-tumorous tissues and normal liver tissues. Low Barx1 expression is correlated with higher tumor-nodule-metastasis stage and indicates poor prognosis...
May 30, 2017: Oncotarget
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