DOCSLIB.ORG

Redalyc.Genetic Polymorphisms of PPAR Gamma, Arsenic Methylation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Redalyc.Genetic Polymorphisms of PPAR Gamma, Arsenic Methylation Salud Pública de México ISSN: 0036-3634 [email protected] Instituto Nacional de Salud Pública México Pineda-Belmontes, Cristina P; Hernández-Ramírez, Raúl U; Hernández-Alcaraz, César; Cebrián, Mariano E; López-Carrillo, Lizbeth Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women Salud Pública de México, vol. 58, núm. 2, marzo-abril, 2016, pp. 220-227 Instituto Nacional de Salud Pública Cuernavaca, México Available in: http://www.redalyc.org/articulo.oa?id=10645277015 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative ARTÍCULO ORIGINAL Pineda-Belmontes CP y col. Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women Cristina P Pineda-Belmontes, MHS,(1) Raúl U Hernández-Ramírez, MHS,(1) César Hernández-Alcaraz, MHS,(1) Mariano E Cebrián, PhD,(2) Lizbeth López-Carrillo, DPH.(1) Pineda-Belmontes CP, Hernández-Ramírez RU, Pineda-Belmontes CP, Hernández-Ramírez RU, Hernández-Alcaraz C, Cebrián ME, López-Carrillo L. Hernández-Alcaraz C, Cebrián ME, López-Carrillo L. Genetic polymorphisms of PPAR gamma, Polimorfismos genéticos de PPAR gamma, capacidad arsenic methylation capacity and breast de metilación del arsénico y riesgo de cáncer de mama cancer risk in Mexican women. en mujeres mexicanas. Salud Publica Mex 2016;58:220-227. Salud Publica Mex 2016;58:220-227. Abstract Resumen Objective. To evaluate whether the presence of polymor- Objetivo. Evaluar si la presencia de polimorfismos dePPAR γ phisms of peroxisome proliferator-activated receptor gamma (Pro12Ala) y PPARGC1B (Ala203Pro) modifica la asociación PPARγ (Pro12Ala) and PPARGC1B (Ala203Pro) modifies the entre la capacidad de metilación del arsénico inorgánico association between the inorganic arsenic (iAs) methylation (Asi) y el cáncer de mama (CM). Material y métodos. capacity and breast cancer (BC). Materials and meth- Se entrevistaron mujeres mexicanas y recolectaron muestras ods. Mexican women were interviewed, and blood and urine de sangre y orina de (casos/controles=197/220). La concen- samples were collected from them (cases/controls= 197/220). tración de especies de arsénico urinario y los polimorfismos The concentration of urinary arsenic species and the poly- de interés se determinaron mediante cromatografía líquida morphisms of interest were determined by high-performance de alta resolución acoplada a espectrometría de masas liquid chromatography with inductively coupled plasma mass (HPLC-ICP-MS) y reacción en cadena de la polimerasa (PCR), spectrometry (HPLC-ICP-MS) and polymerase chain reaction respectivamente. Resultados. En mujeres con %MMA (PCR), respectively. Results. In women with a high %MMA (monometilarsénico urinario) y razón de primera metila- (urinary monomethyl arsenic) and high primary methylation ción altas (PM=MMA/Asi) se incrementó el riesgo de CM ratio (PM = MMA/iAs), the risk of BC was increased (odds (RM%MMAT3vsT1=3.60: intervalo de confianza [IC]95%2.02- ratio [OR]%MMA T3vs.T1= 3.60: 95% confidence interval [CI] 6.41, RMPMT3vs.T1=3.47:IC95%1.95-6.17), que se mantuvo, 2.02-6.41, ORPMI T3vs.T1= 3.47: 95%CI 1.95-6.17), which was respectivamente, al ajustar por polimorfismos. No se obser- maintained after adjusting for polymorphisms. No significant varon interacciones significativas entre los polimorfismos y interactions were observed between the polymorphisms las variables arsenicales sobre el riesgo de CM. Conclusión. and the arsenic variables on the risk of BC. Conclusion. Los polimorfismos Pro12Ala y Ala203Pro no modificaron la Pro12Ala and Ala203Pro polymorphisms did not modify the asociación entre la capacidad de metilación del Asi y el CM. association between the iAs methylation capacity and BC. Keywords: breast cancer; arsenic; genetic polymorphisms; Palabras clave: cáncer de mama; arsénico; polimorfismos PPARγ; Mexico genéticos; PPARγ; México (1) Instituto Nacional de Salud Pública. Cuernavaca, México. (2) Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional. Ciudad de México, México. Received on: January 16, 2013 • Accepted on: July 6, 2014 Corresponding author: Dra. Lizbeth López Carrillo. Instituto Nacional de Salud Pública. Av. Universidad 655, col. Santa María Ahuacatitlán. 62100 Cuernavaca, Morelos, México. Email: [email protected] 220 salud pública de méxico / vol. 58, no. 2, marzo-abril de 2016 PPAR gamma, arsenic and breast cancer ARTÍCULO ORIGINAL he activation of peroxisome proliferator-activated this type of cancer.16 Additionally, during in vitro tests, receptor gamma (PPARγ) consistently induces iAs interferes with adipogenesis signaling by reducing Tapoptosis, inhibits cellular proliferation, and promotes the expression of PPARγ17,18 and consequently affects cellular differentiation in both hormone-dependent and the balance of cellular proliferation and differentiation hormone-independent mammary tumors.1-5 PPARγ is a in breast, colon, and prostate tumors.17 Additionally, ligand-dependent transcription factor that belongs to iAs can act as an endocrine disruptor and can thus be the superfamily of nuclear hormone receptors (estrogen, considered related to BC by means of the overexpres- progesterone). Ligands modulate PPARγ functions, sion of aromatase, an enzyme that limits the rate of thereby releasing receptor corepressors and permitting estrogen synthesis.19 The expression of this enzyme can binding of coactivators, which facilitates its transacti- be inhibited by PPARγ activation via the overexpression vation.6 An important gene in said transactivation of of BRCA1 (tumor suppressor gene) and the inhibition of PPARγ is PPARγ coactivator 1 beta (PPARGC1B), which PGE2 (proinflammatory prostaglandin E2).20 can also bind to and activate the α and β estrogen recep- In accordance with the preceding findings, the ob- tors (ERs) in vitro in a ligand-independent manner, with jective of this study is to evaluate whether the previously greater affinity for ERβ.7 observed association between the methylation capacity Genetic variants of these genes, Pro12Ala of the of iAs and BC is modified according to the presence of PPARγ gene and Ala203Pro of the PPARGC1B gene, have the Pro12Ala polymorphism of the PPARγ gene and the been evaluated in relation to the risk of breast cancer Ala203Pro polymorphism of the PPARGC1B gene in (BC) in previous epidemiological studies. Evidence Mexican women, considering that BC is a major problem that the Pro12Ala polymorphism of the PPARγ gene is not only in Mexico but also in Latin America.21 related to BC is contradictory. In two studies conducted, one in Taiwanese women and the other in the cohort of Materials and methods the Nurses’ Health Study, no significant associations between the Pro12Ala variant and BC were found.3,8 In Study population contrast, in a prospective study in the USA, a margin- ally significant increased risk of BC was detected in During the period from 2007 to 2011, a case-control study homozygous carriers of the G allele.9 For its part, the was conducted in five northern Mexico states (Chihua- Ala203Pro polymorphism has scarcely been studied in hua, Coahuila, Sonora, Durango, and Nuevo León) relation to BC. Wirtenberger and colleagues reported an where the incidence of BC is higher than elsewhere in increased risk of familial BC for the carriers of the GC the country.14 For the purposes of this report, the first and CC genotypes of Ala203Pro in a German cohort.7 197 cases and 220 recruited controls were included. Li and colleagues, although not evaluating Ala203Pro, The eligibility criteria of the cases were the following: found an increased risk of ER-positive BC in Swedish women with histologically confirmed BC, a minimum and Finnish women who carried risk alleles of several age of 18 years, no history of any other type of cancer, polymorphisms of PPARGC1B.10 Our research group and a minimum of one year of residence in the study confirmed the absence of a significant association be- area. The patients were identified in hospital units (n = tween the Pro12Ala variant of the PPARγ gene and BC 17) of the Mexican Institute of Social Security (Instituto and detected a marginally significant negative associa- Mexicano del Seguro Social – IMSS), Secretary of Health, tion in women who were heterozygous for the Ala203Pro University Hospitals, and the Institute of Security and polymorphism of the PPARGC1B gene.11 Social Services for State Workers (Instituto de Seguridad Recently, our research group has also identified that y Servicios Sociales de los Trabajadores del Estado – ISSSTE) the adult female residents in northern Mexico, who are located in those states. The response rate was 94.8%. exposed to inorganic arsenic (iAs) principally through The controls were healthy women without a his- drinking water12 and food,13 with less capacity for uri- tory of cancer who were matched with the index case nary elimination, evaluated through the percentage of by age (±5 years) and place of residence. Controls were elimination of monomethyl arsenic (%MMA), presented identified in the five aforementioned states, by means an increased risk of BC (Odd Ratio [OR]%MMAQ5vs.Q1= of the master sampling frame of the System of National 2.63; 95% confidence interval [95%CI] 1.89–3.66; p for Health Surveys of Mexico, composed of basic geostatisti- trend < 0.001).14,15 While the mechanisms by which iAs cal areas (BGAs) with square-shaped (20–80) regions in could be a cofactor of BC have not been clearly eluci- urban areas and tracts of approximately 10 000 hectares dated, it has been observed that sodium arsenite mimics with identifiable natural limits in rural areas. The BGAs the effects of estradiol in the BC cell line MCF-7, inducing were randomly selected and, within them, the squares, cellular proliferation, which, in turn, is a risk factor for in which the domiciles were located systematically to salud pública de méxico / vol. 58, no. 2, marzo-abril de 2016 221 ARTÍCULO ORIGINAL Pineda-Belmontes CP y col.
Load more

Recommended publications
  • The Role of Nuclear Lamin B1 in Cell Proliferation and Senescence
    Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press The role of nuclear lamin B1 in cell proliferation and senescence Takeshi Shimi,1 Veronika Butin-Israeli,1 Stephen A. Adam,1 Robert B. Hamanaka,2 Anne E. Goldman,1 Catherine A. Lucas,1 Dale K. Shumaker,1 Steven T. Kosak,1 Navdeep S. Chandel,2 and Robert D. Goldman1,3 1Department of Cell and Molecular Biology, 2Department of Medicine, Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions. The results of this study demonstrate that LB1 expression in WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also decreases LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism. Silencing the expression of LB1 slows cell proliferation and induces premature senescence in WI-38 cells. The effects of LB1 silencing on proliferation require the activation of p53, but not pRb. However, the induction of premature senescence requires both p53 and pRb. The proliferation defects induced by silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial reactive oxygen species (ROS), which can be rescued by growth under hypoxic conditions. In contrast to the effects of LB1 silencing, overexpression of LB1 increases the proliferation rate and delays the onset of senescence of WI-38 cells. This overexpression eventually leads to cell cycle arrest at the G1/S boundary.
    [Show full text]
  • Supplementary Materials: Evaluation of Cytotoxicity and Α-Glucosidase Inhibitory Activity of Amide and Polyamino-Derivatives of Lupane Triterpenoids
    Supplementary Materials: Evaluation of cytotoxicity and α-glucosidase inhibitory activity of amide and polyamino-derivatives of lupane triterpenoids Oxana B. Kazakova1*, Gul'nara V. Giniyatullina1, Akhat G. Mustafin1, Denis A. Babkov2, Elena V. Sokolova2, Alexander A. Spasov2* 1Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, 71, pr. Oktyabrya, 450054 Ufa, Russian Federation 2Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya st. 39, Volgograd 400087, Russian Federation Correspondence Prof. Dr. Oxana B. Kazakova Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences 71 Prospeсt Oktyabrya Ufa, 450054 Russian Federation E-mail: [email protected] Prof. Dr. Alexander A. Spasov Scientific Center for Innovative Drugs of the Volgograd State Medical University 39 Novorossiyskaya st. Volgograd, 400087 Russian Federation E-mail: [email protected] Figure S1. 1H and 13C of compound 2. H NH N H O H O H 2 2 Figure S2. 1H and 13C of compound 4. NH2 O H O H CH3 O O H H3C O H 4 3 Figure S3. Anticancer screening data of compound 2 at single dose assay 4 Figure S4. Anticancer screening data of compound 7 at single dose assay 5 Figure S5. Anticancer screening data of compound 8 at single dose assay 6 Figure S6. Anticancer screening data of compound 9 at single dose assay 7 Figure S7. Anticancer screening data of compound 12 at single dose assay 8 Figure S8. Anticancer screening data of compound 13 at single dose assay 9 Figure S9. Anticancer screening data of compound 14 at single dose assay 10 Figure S10.
    [Show full text]
  • Identification of Key Candidate Genes and Molecular Pathways in White Fat
    Pan et al. Human Genomics (2019) 13:55 https://doi.org/10.1186/s40246-019-0239-x PRIMARY RESEARCH Open Access Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology Yuyan Pan, Jiaqi Liu* and Fazhi Qi* Abstract Background: Obesity—with its increased risk of obesity-associated metabolic diseases—has become one of the greatest public health epidemics of the twenty-first century in affluent countries. To date, there are no ideal drugs for treating obesity. Studies have shown that activation of brown adipose tissue (BAT) can promote energy consumption and inhibit obesity, which makes browning of white adipose tissue (WAT) a potential therapeutic target for obesity. Our objective was to identify genes and molecular pathways associated with WAT and the activation of BAT to WAT browning, by using publicly available data and computational tools; this knowledge might help in targeting relevant signaling pathways for treating obesity and other related metabolic diseases. Results: In this study, we used text mining to find out genes related to brown fat and white fat browning. Combined with biological process and pathway analysis in GeneCodis and protein-protein interaction analysis by using STRING and Cytoscape, a list of high priority target genes was developed. The Human Protein Atlas was used to analyze protein expression. Candidate drugs were derived on the basis of the drug-gene interaction analysis of the final genes. Our study identified 18 genes representing 6 different pathways, targetable by a total of 33 drugs as possible drug treatments. The final list included 18 peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, 4 beta 3 adrenoceptor (β3-AR) agonists, 1 insulin sensitizer, 3 insulins, 6 lipase clearing factor stimulants and other drugs.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Relationship of PPARG, PPARGC1A, and PPARGC1B Polymorphisms with Susceptibility to Hepatocellular Carcinoma in an Eastern Chinese Han Population
    Journal name: OncoTargets and Therapy Article Designation: Original Research Year: 2018 Volume: 11 OncoTargets and Therapy Dovepress Running head verso: Zhang et al Running head recto: PPARG, PPARGC1A, and PPARGC1B SNPs and HCC open access to scientific and medical research DOI: 168274 Open Access Full Text Article ORIGINAL RESEARCH Relationship of PPARG, PPARGC1A, and PPARGC1B polymorphisms with susceptibility to hepatocellular carcinoma in an eastern Chinese Han population Sheng Zhang,1,* Jiakai Jiang,1,* Background: PPARG, PPARGC1A, and PPARGC1B polymorphisms may be implicated in Zhan Chen,2 Yafeng Wang,3 the development of cancer. Weifeng Tang,4 Yu Chen,5–7 Participants and methods: In this study, we selected PPARG rs1801282 C.G and rs3856806 Longgen Liu8 C.T, PPARGC1A rs2970847 C.T, and PPARGC1B rs7732671 G.C and rs17572019 G.A single-nucleotide polymorphisms to explore the relationship between these polymorphisms 1Department of General Surgery, Changzhou Third People’s Hospital, and hepatocellular carcinoma (HCC) risk. A total of 584 HCC patients and 923 controls were Changzhou, Jiangsu Province, China; enrolled. 2Department of Thoracic Surgery, Fujian Medical University Union Results: We found that PPARG rs1801282 C.G polymorphism was correlated with a decreased Hospital, Fuzhou, Fujian Province, susceptibility of HCC (CG vs CC, adjusted OR 0.47, 95% CI 0.27–0.82, P=0.007; CG/GG vs CC, China; 3Department of Cardiology, People’s Hospital of Xishuangbanna adjusted OR 0.52, 95% CI 0.31–0.88, P=0.015). However, PPARG rs3856806 C.T polymorphism Dai Autonomous Prefecture, Jinghong, was a risk factor for HCC (TT vs CC, adjusted OR 2.33, 95% CI 1.25–4.36, P=0.008; TT vs CT/CC, 4 Yunnan Province, China; Department adjusted OR 2.26, 95% CI 1.22–4.17, P 0.010).
    [Show full text]
  • Genetic Variants in PPARGC1B and CNTN4 Are
    *Abstract, Title Page, Manuscript, References, Legends 1 Full Title: Genetic Variants in PPARGC1B and CNTN4 are Associated with Thromboxane A2 Formation 1 2 and with Cardiovascular Event Free Survival in the Anglo-Scandinavian Cardiac Outcomes Trial 3 4 5 (ASCOT). 6 7 8 9 First author's surname and running title: McCarthy; Genetic associations with Thromboxane A 10 2 11 12 13 14 Authors: McCarthy NS1,2, Vangjeli C1, Surendran P1,3, Treumann A4, Rooney C1, Ho E1, Sever P5, Thom 15 16 S5, Hughes AD5, Munroe PB6, Howard P6, Johnson T6,7, Caulfield M6, Shields DC3, O’Brien E3, Fitzgerald 17 18 3 1 19 DJ , Stanton AV . 20 21 22 23 1 24 Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, RCSI, Dublin, Ireland 25 26 2Centre for the Genetic Origins of Health and Disease, University of Western Australia, Perth, 27 28 Australia 29 30 3 31 School of Medicine, UCD Conway Institute, University College Dublin, Dublin. 32 33 4Newcastle University Protein and Proteome Analysis (NUPPA), University of Newcastle, Newcastle 34 35 upon Tyne, United Kingdom 36 37 5 38 International Centre for Circulatory Health, Imperial College London, London, UK 39 40 6Clinical Pharmacology, William Harvey Research Institute, Barts and the London Medical School, 41 42 43 Queen Mary University of London and NIHR Barts Cardiovascular Biomedical Research Unit, London, 44 45 UK 46 47 7GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK 48 49 50 51 52 Corresponding author address: 53 54 Name: Nina S. McCarthy 55 56 57 Street Address: 58 59 Centre for the Genetic Origins of Health and Disease, Level 5, 60 61 62 63 64 65 2 MRF Building, 1 2 50 Murray St, 3 4 5 WA 6000 6 7 Australia 8 9 Tel: +61(0)424567369 10 11 12 Email: [email protected] 13 14 15 16 Total Word Count: 3,822 (incl abstract, text, tables and figures legends) 17 18 19 Number of Figures: 2 20 21 Number of Tables: 3 22 23 24 Number of Supplementary Files: 1 25 26 27 28 Journal Subject Terms: 29 30 31 1.
    [Show full text]
  • Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
    BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in
    [Show full text]
  • Supplementary Table 1
    Supplementary Table 1. 492 genes are unique to 0 h post-heat timepoint. The name, p-value, fold change, location and family of each gene are indicated. Genes were filtered for an absolute value log2 ration 1.5 and a significance value of p ≤ 0.05. Symbol p-value Log Gene Name Location Family Ratio ABCA13 1.87E-02 3.292 ATP-binding cassette, sub-family unknown transporter A (ABC1), member 13 ABCB1 1.93E-02 −1.819 ATP-binding cassette, sub-family Plasma transporter B (MDR/TAP), member 1 Membrane ABCC3 2.83E-02 2.016 ATP-binding cassette, sub-family Plasma transporter C (CFTR/MRP), member 3 Membrane ABHD6 7.79E-03 −2.717 abhydrolase domain containing 6 Cytoplasm enzyme ACAT1 4.10E-02 3.009 acetyl-CoA acetyltransferase 1 Cytoplasm enzyme ACBD4 2.66E-03 1.722 acyl-CoA binding domain unknown other containing 4 ACSL5 1.86E-02 −2.876 acyl-CoA synthetase long-chain Cytoplasm enzyme family member 5 ADAM23 3.33E-02 −3.008 ADAM metallopeptidase domain Plasma peptidase 23 Membrane ADAM29 5.58E-03 3.463 ADAM metallopeptidase domain Plasma peptidase 29 Membrane ADAMTS17 2.67E-04 3.051 ADAM metallopeptidase with Extracellular other thrombospondin type 1 motif, 17 Space ADCYAP1R1 1.20E-02 1.848 adenylate cyclase activating Plasma G-protein polypeptide 1 (pituitary) receptor Membrane coupled type I receptor ADH6 (includes 4.02E-02 −1.845 alcohol dehydrogenase 6 (class Cytoplasm enzyme EG:130) V) AHSA2 1.54E-04 −1.6 AHA1, activator of heat shock unknown other 90kDa protein ATPase homolog 2 (yeast) AK5 3.32E-02 1.658 adenylate kinase 5 Cytoplasm kinase AK7
    [Show full text]
  • Hepatocyte Nuclear Factor 4 Alpha (Hnf4α) Activation Is Essential for Termination Of
    bioRxiv preprint doi: https://doi.org/10.1101/304808; this version posted April 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Hepatocyte Nuclear Factor 4 alpha (HNF4α) Activation is Essential for Termination of Liver Regeneration Ian Huck1, Sumedha Gunewardena2, Regina Espanol-Suner3, Holger Willenbring3,4,5 and Udayan Apte1 1Department of Pharmacology, Toxicology and Therapeutics, and 2Department of Biostatistics University of Kansas Medical Center, Kansas City, KS; 3Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research 4Liver Center and 5Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, CA Corresponding Author: Udayan Apte, PhD, DABT Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center 3901 Rainbow Blvd, MS1018 Kansas City, KS 66160 Tel: (913) 588-9247 E-mail: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/304808; this version posted April 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Financial Support: These studies were supported by NIH-COBRE (P20 RR021940-03, P30 GM118247), NIEHS Toxicology Training Grant (T32ES007079-34) and NIH R01DK 0198414 bioRxiv preprint doi: https://doi.org/10.1101/304808; this version posted April 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Hepatocyte Nuclear Factor 4 alpha (HNF4α) is critical for hepatic differentiation.
    [Show full text]
  • Downregulation of Carnitine Acyl-Carnitine Translocase by Mirnas
    Page 1 of 288 Diabetes 1 Downregulation of Carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretion Mufaddal S. Soni1, Mary E. Rabaglia1, Sushant Bhatnagar1, Jin Shang2, Olga Ilkayeva3, Randall Mynatt4, Yun-Ping Zhou2, Eric E. Schadt6, Nancy A.Thornberry2, Deborah M. Muoio5, Mark P. Keller1 and Alan D. Attie1 From the 1Department of Biochemistry, University of Wisconsin, Madison, Wisconsin; 2Department of Metabolic Disorders-Diabetes, Merck Research Laboratories, Rahway, New Jersey; 3Sarah W. Stedman Nutrition and Metabolism Center, Duke Institute of Molecular Physiology, 5Departments of Medicine and Pharmacology and Cancer Biology, Durham, North Carolina. 4Pennington Biomedical Research Center, Louisiana State University system, Baton Rouge, Louisiana; 6Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, New York. Corresponding author Alan D. Attie, 543A Biochemistry Addition, 433 Babcock Drive, Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, (608) 262-1372 (Ph), (608) 263-9608 (fax), [email protected]. Running Title: Fatty acyl-carnitines enhance insulin secretion Abstract word count: 163 Main text Word count: 3960 Number of tables: 0 Number of figures: 5 Diabetes Publish Ahead of Print, published online June 26, 2014 Diabetes Page 2 of 288 2 ABSTRACT We previously demonstrated that micro-RNAs 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of micro-RNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including non-fuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT, Slc25a20) is a direct target of these miRNAs.
    [Show full text]
  • Genetic Variation of ESR1 and Its Co-Activator PPARGC1B Is
    Li et al. Breast Cancer Research 2011, 13:R10 http://breast-cancer-research.com/content/13/1/R10 RESEARCHARTICLE Open Access Genetic variation of ESR1 and its co-activator PPARGC1B is synergistic in augmenting the risk of estrogen receptor-positive breast cancer Yuqing Li1,YiLi1, Sara Wedrén2, Guoliang Li3, Tze Howe Charn4, Kartiki Vasant Desai4, Carine Bonnard5, Kamila Czene6, Keith Humphreys6, Hatef Darabi6, Kristjana Einarsdóttir7, Tuomas Heikkinen8, Kristiina Aittomäki9, Carl Blomqvist10, Kee Seng Chia11, Heli Nevanlinna8, Per Hall6, Edison T Liu4, Jianjun Liu1* Abstract Introduction: Given the role of estrogen in breast carcinogenesis and the modification of estrogen receptor (ER) activity by its biochemical cofactors, we hypothesize that genetic variation within ER cofactor genes alters cellular response to estrogen exposure and consequently modifies the risk for ER-positive breast cancer. Methods: We genotyped 790 tagging SNPs within 60 ER cofactor genes in 1,257 cases and 1,464 controls from Sweden and in 2,215 cases and 1,265 controls from Finland, and tested their associations with either ER-positive or ER-negative breast cancer. Results: Seven SNPs showed consistent association with ER-positive breast cancer in the two independent samples, and six of them were located within PPARGC1B, encoding an ER co-activator, with the strongest association at rs741581 (odds ratio = 1.41, P = 4.84 × 10-5) that survived Bonferroni correction for multiple testing in the combined ER-positive breast cancer sample (Pcorrected = 0.03). Moreover, we also observed significant synergistic interaction (Pinteraction = 0.008) between the genetic polymorphisms within PPARGC1B and ESR1 in ER- positive breast cancer.
    [Show full text]
  • CREB-Dependent Transcription in Astrocytes: Signalling Pathways, Gene Profiles and Neuroprotective Role in Brain Injury
    CREB-dependent transcription in astrocytes: signalling pathways, gene profiles and neuroprotective role in brain injury. Tesis doctoral Luis Pardo Fernández Bellaterra, Septiembre 2015 Instituto de Neurociencias Departamento de Bioquímica i Biologia Molecular Unidad de Bioquímica y Biologia Molecular Facultad de Medicina CREB-dependent transcription in astrocytes: signalling pathways, gene profiles and neuroprotective role in brain injury. Memoria del trabajo experimental para optar al grado de doctor, correspondiente al Programa de Doctorado en Neurociencias del Instituto de Neurociencias de la Universidad Autónoma de Barcelona, llevado a cabo por Luis Pardo Fernández bajo la dirección de la Dra. Elena Galea Rodríguez de Velasco y la Dra. Roser Masgrau Juanola, en el Instituto de Neurociencias de la Universidad Autónoma de Barcelona. Doctorando Directoras de tesis Luis Pardo Fernández Dra. Elena Galea Dra. Roser Masgrau In memoriam María Dolores Álvarez Durán Abuela, eres la culpable de que haya decidido recorrer el camino de la ciencia. Que estas líneas ayuden a conservar tu recuerdo. A mis padres y hermanos, A Meri INDEX I Summary 1 II Introduction 3 1 Astrocytes: physiology and pathology 5 1.1 Anatomical organization 6 1.2 Origins and heterogeneity 6 1.3 Astrocyte functions 8 1.3.1 Developmental functions 8 1.3.2 Neurovascular functions 9 1.3.3 Metabolic support 11 1.3.4 Homeostatic functions 13 1.3.5 Antioxidant functions 15 1.3.6 Signalling functions 15 1.4 Astrocytes in brain pathology 20 1.5 Reactive astrogliosis 22 2 The transcription
    [Show full text]