Molecular characterization of an adiponectin receptor homolog in the white leg shrimp, Litopenaeus vannamei

Adiponectin (AdipoQ) and its receptors (AdipoRs) are strongly related to growth and development of skeletal muscle, as well as glucose and lipid metabolism in vertebrates. Herein we report the identification of the first full-length cDNA encoding an AdipoR homolog (Liv-AdipoR) from the decapod crustacean Litopenaeus vannamei using a combination of next generation sequencing (NGS) technology and bioinformatics analysis. The full-length Liv-AdipoR (1,245 bp) encoded a protein that exhibited the canonical seven transmembrane domains (7TMs) and the inversed topology that characterize members of the progestin and adipoQ receptor (PAQR) family. Based on the obtained sequence information, only a single orthologous AdipoR gene appears to exist in arthropods, whereas two paralogs, AdipoR1 and AdipoR2, have evolved in vertebrates. Transcriptional analysis suggested that the single Liv-AdipoR gene appears to serve the functions of two mammalian AdipoRs. At 72 h after injection of 50 pmol Liv-AdipoR dsRNA (340 bp) into L. vannamei thoracic muscle and deep abdominal muscle, transcription levels of Liv-AdipoR decreased by 93% and 97%, respectively. This confirmed optimal conditions for RNAi of Liv-AdipoR. Knockdown of Liv-AdipoR resulted in significant changes in the plasma levels of ammonia, 3-methylhistine, and ornithine, but not plasma glucose, suggesting that that Liv-AdipoR is important for maintaining muscle fibers. The chronic effect of Liv-AdipoR dsRNA injection was increased mortality. Transcriptomic analysis showed that 804 contigs were upregulated and 212 contigs were downregulated by the knockdown of Liv-AdipoR in deep abdominal muscle. The significantly upregulated genes were categorized as four main functional groups: RNA-editing and transcriptional regulators, molecular chaperones, metabolic regulators, and channel proteins

Effect of single nucleotide polymorphisms within the interleukin-4 promoter on aspirin intolerance in asthmatics and interleukin-4 promoter activity

Objective Aspirin affects interleukin-4 (IL-4) synthesis; however, the genetic role of IL-4 has not been evaluated in asthmatics with aspirin hypersensitivity. The objective of the study was to examine the influence of single nucleotide polymorphisms (SNPs) in IL-4 gene on aspirin hypersensitivity in asthmatics at the genetic and molecular levels. Methods Aspirin-intolerant (AIA, n = 103) and aspirintolerant asthmatics (n = 270) were genotyped and functional promoter assays were performed. Results Of 15 SNPs tested, seven (-589T>C (rs2243250) in promoter, -33T>C (rs2070874) in the 50-untranslated region, +4047A>G (rs2243266), +4144C>G (rs2243267), +4221C>A (rs2243268), +4367G>A (rs2243270), and +5090A>G (rs2243274) in introns) were significantly associated with AIA risk. The frequency of the rare allele (C) of -589T>C was higher in the AIA group than in the aspirin-tolerant asthmatic group (P(corr) = 0.016), and a gene dose-dependent decline in forced expiratory volume in 1 s was noted after an aspirin challenge (P = 0.0009). Aspirin unregulated IL-4 mRNA production in Jurkat T and K562 leukemia cells. A reporter plasmid assay revealed that aspirin augmented IL-4 promoter transactivation with the -589T>C C and -33T>C C alleles, compared with that bearing the -589T>C T and -33T>C T alleles. Further, electrophoretic mobility shift assay showed the formation of nuclear complexes with -33T>C and -589T>C allele-containing probes; this was augmented by aspirin. The complexes formed with the -33T>C and -589T>C probes were shifted by treatment with anti-CCAAT-enhancer-binding proteins beta and anti-nuclear factor of activated T-cells antibodies, respectively, indicating the inclusion of these transcription factors. Conclusion Aspirin may regulate IL4 expression in an allele-specific manner by altering the availability of transcription factors to the key regulatory elements in the IL4 promoter, leading to aspirin hypersensitivity. Pharmacogenetics and Genomics 20:748-758 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.This study was supported by the BK21, Korea Research Foundation to B.S.K. and J.H.K., partially; and the Korea Health 21 R&D Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea [A010249].Kim TH, 2008, CLIN EXP ALLERGY, V38, P1727, DOI 10.1111/j.1365-2222.2008.03082.xGuo LY, 2008, J IMMUNOL, V181, P3984Hebenstreit D, 2008, J BIOL CHEM, V283, P22490, DOI 10.1074/jbc.M804096200Cormican LJ, 2005, CLIN EXP ALLERGY, V35, P717, DOI 10.1111/j.1365-2222.2005.02261.xCieslik KA, 2005, J BIOL CHEM, V280, P18411, DOI 10.1074/jbc.M410017200Szefler SJ, 2005, J ALLERGY CLIN IMMUN, V115, P233, DOI 10.1016/j.jaci.2004.11.014Adjers K, 2005, INT ARCH ALLERGY IMM, V138, P251, DOI 10.1159/000088726Basehore MJ, 2004, J ALLERGY CLIN IMMUN, V114, P80, DOI 10.1016/j.jaci.2004.05.035Pagani F, 2004, NAT REV GENET, V5, P389, DOI 10.1038/nrg1327Nyholt DR, 2004, AM J HUM GENET, V74, P765Mifflin RC, 2004, MOL PHARMACOL, V65, P470Cohn L, 2004, ANNU REV IMMUNOL, V22, P789, DOI 10.1146/annurev.immunol.22.012703.104716Li-Weber M, 2003, NAT REV IMMUNOL, V3, P534, DOI 10.1038/nri1128Szczeklik A, 2003, J ALLERGY CLIN IMMUN, V111, P913, DOI 10.1067/mai.2003.1487Sousa AR, 2002, NEW ENGL J MED, V347, P1493Nakashima H, 2002, GENES IMMUN, V3, P107, DOI 10.1038/sj/gene/6363820Dahlen SE, 2002, AM J RESP CRIT CARE, V165, P9OLIPHANT A, 2002, BIOTECHNIQUES S, V32, P56*GINA, 2002, GLOB STRAT ASTHM MANPEREZ GM, 2002, J IMMUNOL, V168, P1428Tegeder I, 2001, FASEB J, V15, P2057Stevenson DD, 2001, ANN ALLERG ASTHMA IM, V87, P177Stephens M, 2001, AM J HUM GENET, V68, P978Cianferoni A, 2001, BLOOD, V97, P1742Leff AR, 2001, ANNU REV MED, V52, P1Suzuki I, 2000, CLIN EXP ALLERGY, V30, P1746Berberich-Siebelt F, 2000, EUR J IMMUNOL, V30, P2576Kauffmann F, 1999, CLIN EXP ALLERGY, V29, P17Wiesch DG, 1999, J ALLERGY CLIN IMMUN, V104, P895Varga EM, 1999, EUR RESPIR J, V14, P610Burchard EG, 1999, AM J RESP CRIT CARE, V160, P919Schwenger P, 1999, J CELL PHYSIOL, V179, P109Drazen JM, 1999, NEW ENGL J MED, V340, P197Gerli R, 1998, BLOOD, V92, P2389Noguchi E, 1998, CLIN EXP ALLERGY, V28, P449Dong ZG, 1997, J BIOL CHEM, V272, P9962Marsh DG, 1997, NAT GENET, V15, P389Walley AJ, 1996, J MED GENET, V33, P689Klein SC, 1996, CELL IMMUNOL, V167, P259DAVYDOV IV, 1995, J IMMUNOL, V155, P5273ROSENWASSER LJ, 1995, CLIN EXP ALLERGY, V25, P74*AM THOR SOC, 1995, AM J RESP CRIT CARE, V152, P1107KOPP E, 1994, SCIENCE, V265, P956CRABTREE GR, 1994, ANNU REV BIOCHEM, V63, P1045FLESCHER E, 1991, J IMMUNOL, V146, P2553AKIRA S, 1990, EMBO J, V9, P1897SZCZEKLIK A, 1990, EUR RESPIR J, V3, P588*SENSORMEDICS, 1988, PULM UT OP MAN PREDHEDRICK PW, 1987, GENETICS, V117, P331MORRIS JF, 1976, WESTERN J MED, V125, P110SAMTER M, 1967, J ALLERGY, V40, P281

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes