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https://www.readbyqxmd.com/read/28526321/effects-of-dehp-and-its-metabolite-mehp-on-insulin-signalling-and-proteins-involved-in-glut4-translocation-in-cultured-l6-myotubes
#1
Mangala Priya Viswanathan, Vigneswari Mullainadhan, Mayilvanan Chinnaiyan, Balasubramanian Karundevi
Di-(2-ethylhexyl)phthalate (DEHP) is the plasticizer used in variety of medical and consumer products to impart structural flexibility. DEHP and its primary metabolite mono-(2-ethyl hexyl)phthalate (MEHP) posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. Experimental and epidemiological data have shown that DEHP affects blood glucose homeostasis. However, direct effect of DEHP and its metabolite MEHP on insulin signal transduction and glucose transporter 4 (GLUT4) translocation remain obscure...
May 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28452018/elucidate-genetic-diversity-and-population-structure-of-olea-europaea-l-germplasm-in-iran-using-aflp-and-irap-molecular-markers
#2
Esmaeil Khaleghi, Karim Sorkheh, Maryam Hosseni Chaleshtori, Sezai Ercisli
Currently, study of the inter and the intra-population genetic disparity was done by use of the 200 Olea europaea L. which is found growing naturally in the nation of Iran, and this study was carried out by AFLP and IRAP markers. The fingerprints that were similar to the AFLP and the IRAP markers were evidence of high concentrations of heterozygosity and this shows that O. europaea L. is primarily the out crossing species. The average percentage of polymorphism is as shown below: 87.15 and 87.38% of the information used in regard to the AFLP and the IRAP, respectively...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28369191/the-rnaseq-er-api-a-gateway-to-systematically-updated-analysis-of-public-rna-seq-data
#3
Robert Petryszak, Nuno A Fonseca, Anja Füllgrabe, Laura Huerta, Maria Keays, Y Amy Tang, Alvis Brazma
Motivation: The exponential growth of publicly available RNA sequencing (RNA-Seq) data poses an increasing challenge to researchers wishing to discover, analyse and store such data, particularly those based in institutions with limited computational resources. EMBL-EBI is in an ideal position to address these challenges and to allow the scientific community easy access to not just raw, but also processed RNA-Seq data. We present a Web service to access the results of a systematically and continually updated standardised alignment as well as gene and exon expression quantification of all public bulk (and in the near future also single-cell) RNA-Seq runs in 264 species in European Nucleotide Archive, using Representational State Transfer...
March 22, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28356324/insulin-regulated-aminopeptidase-inhibitors-do-not-alter-glucose-handling-in-normal-and-diabetic-rat
#4
Anthony L Albiston, Mauricio Cacador, Puspha Sinnayah, Peta Burns, Siew Yeen Chai
Insulin regulated aminopeptidase (IRAP) co-localises with the glucose transporter 4 (GLUT4) in GLUT4 storage vesicles (GSV) in insulin-responsive cells. In response to insulin, IRAP is the only transmembrane enzyme known to translocate together with GLUT4 to the plasma membrane in adipocytes and muscle cells. Although the intracellular region of IRAP is associated with GLUT4 vesicle trafficking, the role of the aminopeptidase activity in insulin responsive cells has not been elucidated. The aim of this study was to investigate whether the inhibition of the aminopeptidase activity of IRAP facilitates glucose uptake in insulin responsive cells...
March 29, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28328206/ligand-induced-conformational-change-of-insulin-regulated-aminopeptidase-insights-on-catalytic-mechanism-and-active-site-plasticity
#5
Anastasia Mpakali, Emmanuel Saridakis, Karl Harlos, Yuguang Zhao, Paraskevi Kokkala, Dimitris Georgiadis, Petros Giastas, Athanasios Papakyriakou, Efstratios Stratikos
Insulin-regulated aminopeptidase (IRAP) is an enzyme with several important biological functions that is known to process a large variety of different peptidic substrates, although the mechanism behind this wide specificity is not clearly understood. We describe a crystal structure of IRAP in complex with a recently developed bioactive and selective inhibitor at 2.53 Å resolution. In the presence of this inhibitor, the enzyme adopts a novel conformation in which domains II and IV are juxtaposed, forming a hollow structure that excludes external solvent access to the catalytic center...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28319098/irap-endosomes-restrict-tlr9-activation-and-signaling
#6
Joel Babdor, Delphyne Descamps, Aimé Cézaire Adiko, Mira Tohmé, Sophia Maschalidi, Irini Evnouchidou, Luiz Ricardo Vasconcellos, Mariacristina De Luca, Francois-Xavier Mauvais, Meriem Garfa-Traore, Melanie M Brinkmann, Michel Chignard, Bénédicte Manoury, Loredana Saveanu
The retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP(+) endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP(+) endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28213512/27-hydroxycholesterol-impairs-neuronal-glucose-uptake-through-an-irap-glut4-system-dysregulation
#7
Muhammad-Al-Mustafa Ismail, Laura Mateos, Silvia Maioli, Paula Merino-Serrais, Zeina Ali, Maria Lodeiro, Eric Westman, Eran Leitersdorf, Balázs Gulyás, Lars Olof-Wahlund, Bengt Winblad, Irina Savitcheva, Ingemar Björkhem, Angel Cedazo-Mínguez
Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced (18)F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)-mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N)...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28069385/changes-of-renin-angiotensin-system-related-aminopeptidases-in-early-stage-alzheimer-s-disease
#8
Paul Richard Gard, Sara Fidalgo, Isabelle Lotter, Cassandra Richardson, Nicolas Farina, Jennifer Rusted, Naji Tabet
Activities of aminopeptidases A, B, and N (ApA, ApB & ApN) and insulin-regulated aminopeptidase (IRAP) have been seen to be decreased amongst patients with Alzheimer's disease (AD). All of these enzymes are involved with the brain renin-angiotensin system which is believed to be involved with learning and memory. This study aimed to explore the time course and the mechanisms underlying these changes. Serum samples were collected from 45 AD patients at the start of the study, and again 13months later (n=37)...
March 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28035472/insulin-regulated-aminopeptidase-immunoreactivity-is-abundantly-present-in-human-hypothalamus-and-posterior-pituitary-gland-with-reduced-expression-in-paraventricular-and-suprachiasmatic-neurons-in-chronic-schizophrenia
#9
Hans-Gert Bernstein, Susan Müller, Hendrik Dobrowolny, Carmen Wolke, Uwe Lendeckel, Alicja Bukowska, Gerburg Keilhoff, Axel Becker, Kurt Trübner, Johann Steiner, Bernhard Bogerts
The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls...
December 29, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/27936390/irap-inhibition-using-hfi419-prevents-moderate-to-severe-acetylcholine-mediated-vasoconstriction-in-a-rabbit-model
#10
Aisha El-Hawli, Tawar Qaradakhi, Alan Hayes, Emma Rybalka, Renee Smith, Martin Caprnda, Radka Opatrilova, Katarina Gazdikova, Maria Benckova, Peter Kruzliak, Anthony Zulli
Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27834335/a-pcr-rflp-method-for-detection-of-the-lnpep-encoding-human-insulin-regulated-aminopeptidase-irap-rs4869317-polymorphism
#11
MarIa Jesús RamIrez-Expósito, Jos Manuel MartInez-Martos, Teresa Palomeque, Pedro Lorite
BACKGROUND & OBJECTIVES: Insulin regulated aminopeptidase (IRAP) has been related to certain pathologies such as breast cancer, Alzheimer΄s disease and septic shock. IRAP is encoded by the leucyl/cystinyl aminopeptidase (LNPEP) gene. The genetic variation in the LNPEP gene has been analyzed in relation with the mortality and vasopressin clearance in septic shock. The LNPEP rs4869317 SNP (single nucleotide polymorphism) was the most significantly associated SNP with vasopressinase activity, being TT genotype associated with increased mortality...
July 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/27769857/staurosporine-as-an-agonist-for-induction-of-glut4-translocation-identified-by-a-ph-sensitive-fluorescent-irap-morange2-probe
#12
Yufeng Li, Zheng Li, Dan Wang, Xiang Zhang, Jia Li, Sher Ali, Jingze Lu, Hao Zong, Xiaolan Xu
Insulin-stimulated GLUT4 translocation from GLUT4 storage vesicles (GSVs) to the plasma membrane (PM) constitutes a key process for blood glucose control. Therefore, compounds that could promote GLUT4 translocation into the PM represent potential drugs for the treatment of diabetes. In this research, we screened for agonists that induce GLUT4 translocation by using a novel pH-sensitive fluorescent probe, insulin-regulated aminopeptidase (IRAP)-mOrange2. We identified as well as validated one agonist, staurosporine, from a 64,000 compound library...
October 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27734175/a-deeper-look-at-implicit-weight-bias-in-medical-students
#13
Timothy K Baker, Gregory S Smith, Negar Nicole Jacobs, Ramona Houmanfar, Robbyn Tolles, Deborah Kuhls, Melissa Piasecki
The Implicit Relational Assessment Procedure (IRAP, Barnes-Holmes et al. in Psychol Rec 60:527-542, 2010) was utilized as a relatively new tool to measure implicit weight bias in first- and third-year medical students. To date, only two studies (Miller et al. in Acad Med 88:978-982, 2013; Phelan et al. in Med Educ 49:983-992, 2015) have investigated implicit weight bias with medical students and both have found pro-thin/anti-fat implicit attitudes, on average, using the Implicit Association Test (IAT, Greenwald and Banaji in Psychol Rev 102:4-27, 1995) as the assessment tool...
October 12, 2016: Advances in Health Sciences Education: Theory and Practice
https://www.readbyqxmd.com/read/27713012/forebrain-neurone-specific-deletion-of-insulin-regulated-aminopeptidase-causes-age-related-deficits-in-memory
#14
Holly R Yeatman, Anthony L Albiston, Peta Burns, Siew Yeen Chai
Central infusion of Insulin-Regulated Aminopeptidase (IRAP) inhibitors improves memory in both normal rodents and in models of memory deficit. However, in contrast, the global IRAP knockout mice (KO) demonstrate age-accelerated spatial memory deficits and no improvements in performance in any memory tasks. Potentially, the observed memory deficit could be due to the absence of IRAP in the developing brain. We therefore generated a postnatal forebrain neuron-specific IRAP knockout mouse line (CamKIIalphaCre; IRAPlox/lox)...
December 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27606886/sex-difference-in-oxytocin-induced-anti-hyperalgesia-at-the-spinal-level-in-rats-with-intraplantar-carrageenan-induced-inflammation
#15
Lok-Hi Chow, Yuan-Hao Chen, Wan-Chuan Wu, En-Pei Chang, Eagle Yi-Kung Huang
Previously, we demonstrated intrathecal administration of oxytocin strongly induced anti-hyperalgesia in male rats. By using an oxytocin-receptor antagonist (atosiban), the descending oxytocinergic pathway was found to regulate inflammatory hyperalgesia in our previous study using male rats. The activity of this neural pathway is elevated during hyperalgesia, but whether this effect differs in a sex-dependent manner remains unknown. We conducted plantar tests on adult male and female virgin rats in which paw inflammation was induced using carrageenan...
2016: PloS One
https://www.readbyqxmd.com/read/27606717/optimization-and-structure-activity-relationships-of-phosphinic-pseudotripeptide-inhibitors-of-aminopeptidases-that-generate-antigenic-peptides
#16
Paraskevi Kokkala, Anastasia Mpakali, Francois-Xavier Mauvais, Athanasios Papakyriakou, Ira Daskalaki, Ioanna Petropoulou, Sofia Kavvalou, Mirto Papathanasopoulou, Stefanos Agrotis, Theodora-Markisia Fonsou, Peter van Endert, Efstratios Stratikos, Dimitris Georgiadis
The oxytocinase subfamily of M1 aminopeptidases, consisting of ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase (IRAP), plays critical roles in the generation of antigenic peptides and indirectly regulates human adaptive immune responses. We have previously demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors of this group of enzymes. In this study, we used synthetic methodologies able to furnish a series of stereochemically defined phosphinic pseudotripeptides and demonstrate that side chains at P1' and P2' positions are critical determinants in driving potency and selectivity...
October 13, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27588541/implicit-alcohol-related-expectancies-and-the-effect-of-context
#17
Rebecca L Monk, Charlotte R Pennington, Claire Campbell, Alan Price, Derek Heim
OBJECTIVE: The current study examined the impact of varying pictorial cues and testing contexts on implicit alcohol-related expectancies. METHOD: Seventy-six participants were assigned randomly to complete an Implicit Relational Assessment Procedure (IRAP) in either a pub or lecture context. The IRAP exposed participants to pictorial cues that depicted an alcoholic beverage in the foreground of a pub (alcohol-congruent stimuli) or university lecture theater (alcohol-incongruent stimuli), and participants were required to match both positive and negative alcohol-related outcome expectancies to these stimuli...
September 2016: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/27578509/prss1-spink1-cftr-and-ctrc-pathogenic-variants-in-korean-patients-with-idiopathic-pancreatitis
#18
Sun Mi Cho, Saeam Shin, Kyung A Lee
BACKGROUND: This study aimed to identify pathogenic variants of PRSS1, SPINK1, CFTR, and CTRC genes in Korean patients with idiopathic pancreatitis. METHODS: The study population consisted of 116 Korean subjects (65 males, 51 females; mean age, 30.4 yr, range, 1-88 yr) diagnosed with idiopathic chronic pancreatitis (ICP), idiopathic recurrent acute pancreatitis (IRAP), or idiopathic acute pancreatitis (IAP). We analyzed sequences of targeted regions in the PRSS1, SPINK1, CFTR, and CTRC genes, copy numbers of PRSS1 and SPINK1, and clinical data from medical records...
November 2016: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/27501164/aryl-sulfonamide-inhibitors-of-insulin-regulated-aminopeptidase-enhance-spine-density-in-primary-hippocampal-neuron-cultures
#19
Shanti Diwakarla, Erik Nylander, Alfhild Grönbladh, Sudarsana Reddy Vanga, Yasmin Shamsudin Khan, Hugo Gutiérrez-de-Terán, Jonas Sävmarker, Leelee Ng, Vi Pham, Thomas Lundbäck, Annika Jenmalm-Jensen, Richard Svensson, Per Artursson, Sofia Zelleroth, Karin Engen, Ulrika Rosenström, Mats Larhed, Johan Åqvist, Siew Yeen Chai, Mathias Hallberg
The zinc metallopeptidase insulin regulated aminopeptidase (IRAP), which is highly expressed in the hippocampus and other brain regions associated with cognitive function, has been identified as a high-affinity binding site of the hexapeptide angiotensin IV (Ang IV). This hexapeptide is thought to facilitate learning and memory by binding to the catalytic site of IRAP to inhibit its enzymatic activity. In support of this hypothesis, low molecular weight, nonpeptide specific inhibitors of IRAP have been shown to enhance memory in rodent models...
August 8, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27450967/endoscopic-sphincterotomy-es-may-not-alter-the-natural-history-of-idiopathic-recurrent-acute-pancreatitis-irap
#20
MULTICENTER STUDY
Rohit Das, Bridger Clarke, Gong Tang, Georgios I Papachristou, David C Whitcomb, Adam Slivka, Dhiraj Yadav
BACKGROUND: The role of endoscopic sphincterotomy (ES) in idiopathic recurrent acute pancreatitis (IRAP) is unclear. We hypothesized that ES will alter the natural history of IRAP. METHODS: We retrospectively studied the course of 50 IRAP patients from the NAPS2 study from UPMC based on whether they underwent ES or were managed medically. Data included age at first AP, rate of attacks, and history of severe AP. Primary outcomes were any subsequent AP and rate of attacks; secondary outcome was chronic pancreatitis (CP) diagnosis during follow-up...
September 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
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