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Cecon T Mahapatra, Nur P Damayanti, Samuel C Guffey, Jennifer S Serafin, Joseph Irudayaraj, Maria S Sepúlveda
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic fluorinated compounds that are highly bioaccumulative and persistent organic pollutants. Perfluorooctanoic acid (PFOA), an eight-carbon chain perfluorinated carboxylic acid, was used heavily for the production of fluoropolymers, but concerns have led to its replacement by shorter carbon chain homologues such as perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA). However, limited toxicity data exist for these substitutes. We evaluated the toxicity of PFOA, PFHxA and PFBA on a zebrafish liver cell line and investigated the effects of exposure on cell metabolism...
December 5, 2016: Journal of Applied Toxicology: JAT
Rongli Sun, Meng Cao, Juan Zhang, Wenwen Yang, Haiyan Wei, Xing Meng, Lihong Yin, Yuepu Pu
Benzene is a well-known hematotoxic carcinogen that can cause leukemia and a variety of blood disorders. Our previous study indicated that benzene disturbs levels of metabolites in the fatty acid β-oxidation (FAO) pathway, which is crucial for the maintenance and function of hematopoietic and leukemic cells. The present research aims to investigate the effects of benzene on changes in the expression of key enzymes in the FAO pathway in male C3H/He mice. Results showed that benzene exposure caused reduced peripheral white blood cell (WBC), red blood cell (RBC), platelet (Pit) counts, and hemoglobin (Hgb) concentration...
October 31, 2016: International Journal of Environmental Research and Public Health
Anna Puig-Oliveras, Manuel Revilla, Anna Castelló, Ana I Fernández, Josep M Folch, Maria Ballester
The aim of this work is to better understand the genetic mechanisms determining two complex traits affecting porcine meat quality: intramuscular fat (IMF) content and its fatty acid (FA) composition. With this purpose, expression Genome-Wide Association Study (eGWAS) of 45 lipid-related genes associated with meat quality traits in swine muscle (Longissimus dorsi) of 114 Iberian × Landrace backcross animals was performed. The eGWAS identified 241 SNPs associated with 11 genes: ACSM5, CROT, FABP3, FOS, HIF1AN, IGF2, MGLL, NCOA1, PIK3R1, PLA2G12A and PPARA...
2016: Scientific Reports
Stine Ninel Hansen, Natasja Spring Ehlers, Shida Zhu, Mathilde Borg Houlberg Thomsen, Rikke Linnemann Nielsen, Dongbing Liu, Guangbiao Wang, Yong Hou, Xiuqing Zhang, Xun Xu, Lars Bolund, Huanming Yang, Jun Wang, Jose Moreira, Henrik J Ditzel, Nils Brünner, Anne-Sofie Schrohl, Jan Stenvang, Ramneek Gupta
BACKGROUND: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. RESULTS: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing concentrations of docetaxel...
2016: BMC Genomics
Junqin Chen, Martin E Young, John C Chatham, David K Crossman, Louis J Dell'Italia, Anath Shalev
Myocardial fatty acid β-oxidation is critical for the maintenance of energy homeostasis and contractile function in the heart, but its regulation is still not fully understood. While thioredoxin-interacting protein (TXNIP) has recently been implicated in cardiac metabolism and mitochondrial function, its effects on β-oxidation have remained unexplored. Using a new cardiomyocyte-specific TXNIP knockout mouse and working heart perfusion studies, as well as loss- and gain-of-function experiments in rat H9C2 and human AC16 cardiomyocytes, we discovered that TXNIP deficiency promotes myocardial β-oxidation via signaling through a specific microRNA, miR-33a...
July 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Joel Vega-Badillo, Roxana Gutiérrez-Vidal, Hugo A Hernández-Pérez, Hugo Villamil-Ramírez, Paola León-Mimila, Fausto Sánchez-Muñoz, Sofía Morán-Ramos, Elena Larrieta-Carrasco, Itzel Fernández-Silva, Nahúm Méndez-Sánchez, Armando R Tovar, Francisco Campos-Pérez, Teresa Villarreal-Molina, Rogelio Hernández-Pando, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros
BACKGROUND AND AIM: Abnormal cholesterol metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH) and fibrosis. miR-33 and miR-144 regulate adenosine triphosphate binding cassette transporter (ABCA1) and other target genes involved in cholesterol efflux, fatty acid oxidation and inflammation. We explored relationships between non-alcoholic fatty liver disease (NAFLD) and the hepatic expression of ABCA1/ABCG1, as well as other target genes regulated by miR-33 (carnitine O-octanoyltransferase, CROT and hydroxyacyl-CoA-dehydrogenase β-subunit, HADHB) and miR-144 (toll-like receptor-2, TLR2)...
September 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Yun Zheng, Shibei Jiang, Yihui Zhang, Rui Zhang, Daoqing Gong
BACKGROUND: miRNAs are single-stranded, small RNA molecules with a length of 18-25 nucleotides. They bind to the 3' untranslated regions of mRNA transcripts to reduce the translation of these transcripts or to cause their degradation. The roles of these molecules differ in biological processes, such as cell differentiation, proliferation, apoptosis and tumor genesis. miRNA-33 is encoded by the gene introns of proteins that bind sterol-regulatory elements. This molecule cooperates with these proteins to control cholesterol homeostasis, fatty acid levels and the genes that are related to the expression of fat metabolism...
2015: International Journal of Molecular Sciences
Sirui Zhou, Lan Xiong, Pingxing Xie, Amirthagowri Ambalavanan, Cynthia V Bourassa, Alexandre Dionne-Laporte, Dan Spiegelman, Maude Turcotte Gauthier, Edouard Henrion, Ousmane Diallo, Patrick A Dion, Guy A Rouleau
BACKGROUND: Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism...
2015: PloS One
April F Mohanty, Fred M Farin, Theo K Bammler, James W MacDonald, Zahra Afsharinejad, Thomas M Burbacher, David S Siscovick, Michelle A Williams, Daniel A Enquobahrie
BACKGROUND: Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. OBJECTIVES: Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. METHODS: We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region...
April 2015: Environmental Research
Xiaoxue Wang, Xiaoli Mu, Jie Zhang, Qingyu Huang, Ambreen Alamdar, Meiping Tian, Liangpo Liu, Heqing Shen
Chronic arsenic exposure through drinking water threatens public health worldwide. Although its multiorgan toxicity has been reported, the impact of chronic arsenic exposure on the metabolic network remains obscure. In this study, male Sprague Dawley rats were exposed to 0.5, 2 or 10 ppm sodium arsenite for three months. An ultra-high performance liquid chromatography/mass spectrometry based metabolomics approach was utilized to unveil the global metabolic response to chronic arsenic exposure in rats. Distinct serum metabolome profiles were found to be associated with the doses...
March 2015: Metallomics: Integrated Biometal Science
Ho Hyun Nam, Dae Won Jun, Hye Joon Jeon, Jai Sun Lee, Waqar Khalid Saeed, Eun Kyung Kim
AIM: To evaluate the effects of osthol on intrahepatic fat synthesis, β-oxidation, inflammation, and insulin resistance by multifaceted analysis. METHODS: Sprague-Dawley rats (n = 30) were randomly divided into control, non-alcoholic fatty liver disease (NAFLD), and osthol groups. NAFLD and osthol groups were fed with a high-fat diet for 14 wk. After 8 wk of the high-fat diet, the osthol group also received osthol 20 mg/kg orally 5 times/wk. To assess the insulin resistance, oral glucose tolerance was performed at the end of 14 wk...
September 7, 2014: World Journal of Gastroenterology: WJG
Benjamin S Murray, Stéphanie Crot, Sviatlana Siankevich, Paul J Dyson
Severe general toxicity issues blight many chemotherapeutics utilized in the treatment of cancers, resulting in the need for more selective drugs able to exert their biological activity at only the required location(s). Toward this aim, we report the development of an organometallic ruthenium compound, functionalized through a η(6)-bound arene ligand with a bicyclononyne derivative, able to participate in strain-promoted cycloaddition reactions with tetrazines. We show that combination of the ruthenium compound with a ditetrazine in biological media results in the in situ formation of a dinuclear molecule that is more cytotoxic toward cancer cells than the starting mononuclear ruthenium compound and tetrazine components...
September 2, 2014: Inorganic Chemistry
Liwei Chen, Jianhua Zhang, Wei Ning Chen
Fatty acid-derived biofuels and biochemicals can be produced in microbes using β-oxidation pathway engineering. In this study, the β-oxidation pathway of Saccharomyces cerevisiae was engineered to accumulate a higher ratio of medium chain fatty acids (MCFAs) when cells were grown on fatty acid-rich feedstock. For this purpose, the haploid deletion strain Δpox1 was obtained, in which the sole acyl-CoA oxidase encoded by POX1 was deleted. Next, the POX2 gene from Yarrowia lipolytica, which encodes an acyl-CoA oxidase with a preference for long chain acyl-CoAs, was expressed in the Δpox1 strain...
2014: PloS One
Chen-Lu Wu, Shui-Ping Zhao, Bi-Lian Yu
BACKGROUND: Apolipoprotein O (apoO) is a new member of the apolipoprotein family. However, data on its physiological functions are limited and inconsistent. Using a microarray expression analysis, this study explored the function of apoO in liver cells. METHODS: HepG2 cells were treated either with oleic acid or tumor necrosis factor-α for 24 h. mRNA and protein expression of apoO were assessed by quantitative real-time PCR (qRT-PCR) and Western blot respectively...
December 17, 2013: Lipids in Health and Disease
Kelly J Kilpin, Stéphanie Crot, Tina Riedel, Jonathan A Kitchen, Paul J Dyson
Taking advantage of the facile and versatile synthetic properties of 'click' 1,2,3-triazolylidene N-heterocyclic carbenes (tzNHC's), a range of new organometallic Ru(II) and Os(II) arene complexes containing functionalised tzNHC ligands, [M(η(6)-p-cymene)(tzNHC)Cl2] [M = Ru(II), Os(II)], have been synthesised and fully characterised, including the X-ray crystal structure of one of the Os(II) complexes. The tzNHC ligands remain coordinated to the metal centres under relevant physiological conditions, and following binding to the model protein, ubiquitin...
January 21, 2014: Dalton Transactions: An International Journal of Inorganic Chemistry
Patrick Carlson, Rebecca J Van Beneden
Adult zebrafish (Danio rerio) were used to investigate mRNA expression in the liver following 7-day and 21-day exposures to 0, 10, 50, or 500 ppb sodium arsenite. Arsenic exposure has been linked to several human disorders including cancers and cardiovascular and metabolic diseases. Quantitative PCR was employed to determine the mRNA expression of genes involved in cell cycle regulation [cyclin E1 (ccne1), WEE1 A kinase (wee1)], DNA damage repair [breast cancer 2 (brca2)] and lipid transport and metabolism [carnitine O-octanoyltransferase (crot), fatty acid binding protein-3 (fabp3) and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (hmgcs1)]...
August 2014: Aquatic Toxicology
Leigh Goedeke, Frances M Vales-Lara, Michael Fenstermaker, Daniel Cirera-Salinas, Aranzazu Chamorro-Jorganes, Cristina M Ramírez, Julie A Mattison, Rafael de Cabo, Yajaira Suárez, Carlos Fernández-Hernando
hsa-miR-33a and hsa-miR-33b, intronic microRNAs (miRNAs) located within the sterol regulatory element-binding protein 2 and 1 genes (Srebp-2 and -1), respectively, have recently been shown to regulate lipid homeostasis in concert with their host genes. Although the functional role of miR-33a and -b has been highly investigated, the role of their passenger strands, miR-33a* and -b*, remains unclear. Here, we demonstrate that miR-33a* and -b* accumulate to steady-state levels in human, mouse, and nonhuman primate tissues and share a similar lipid metabolism target gene network as their sister strands...
June 2013: Molecular and Cellular Biology
Takahiro Horie, Osamu Baba, Yasuhide Kuwabara, Yoshimasa Chujo, Shin Watanabe, Minako Kinoshita, Masahito Horiguchi, Tomoyuki Nakamura, Kazuhisa Chonabayashi, Masakatsu Hishizawa, Koji Hasegawa, Noriaki Kume, Masayuki Yokode, Toru Kita, Takeshi Kimura, Koh Ono
BACKGROUND: Cholesterol efflux from cells to apolipoprotein A-I (apoA-I) acceptors via the ATP-binding cassette transporters ABCA1 and ABCG1 is thought to be central in the antiatherogenic mechanism. MicroRNA (miR)-33 is known to target ABCA1 and ABCG1 in vivo. METHODS AND RESULTS: We assessed the impact of the genetic loss of miR-33 in a mouse model of atherosclerosis. MiR-33 and apoE double-knockout mice (miR-33(-/-)Apoe(-/-)) showed an increase in circulating HDL-C levels with enhanced cholesterol efflux capacity compared with miR-33(+/+)Apoe(-/-) mice...
December 2012: Journal of the American Heart Association
P Merjonen, L Keltikangas-Järvinen, M Jokela, I Seppälä, L-P Lyytikäinen, L Pulkki-Råback, M Kivimäki, M Elovainio, J Kettunen, S Ripatti, M Kähönen, J Viikari, A Palotie, L Peltonen, O T Raitakari, T Lehtimäki
Hostility is a multidimensional personality trait with changing expression over the life course. We performed a genome-wide association study (GWAS) of the components of hostility in a population-based sample of Finnish men and women for whom a total of 2.5 million single-nucleotide polymorphisms (SNPs) were available through direct or in silico genotyping. Hostility dimensions (anger, cynicism and paranoia) were assessed at four time points over a 15-year interval (age range 15-30 years at phase 1 and 30-45 years at phase 4) in 982-1780 participants depending on the hostility measure...
2011: Translational Psychiatry
Ana María Atria, Maria Teresa Garland, Ricardo Baggio
The title ionic compound, (C(7)H(8)N(3))(2)[Ho(2)(C(4)H(5)O(2))(8)], is constructed from two almost identical independent centrosymmetric anionic dimers balanced by two independent 2-amino-1H-benzimidazol-3-ium (Habim(+)) cations. The asymmetric part of each dimer is made up of one Ho(III) cation and four crotonate (crot or but-2-enoate) anions, two of them acting in a simple η(2)-chelating mode and the remaining two acting in two different μ(2):η(2) fashions, viz. purely bridging and bridging-chelating...
July 2012: Acta Crystallographica. Section C, Crystal Structure Communications
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