15 results on '"Yuk Yin Cheung"'
Search Results
2. DNA methylome changes by estradiol benzoate and bisphenol A links early-life environmental exposures to prostate cancer risk
- Author
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Shu Hua Ye, Mario Medvedovic, Gail S. Prins, Jing Chen, Wan Yee Tang, Ana Cheong, Yuk Yin Cheung, Shuk-Mei Ho, Xiang Zhang, and Yuet-Kin Leung
- Subjects
Male ,0301 basic medicine ,endocrine-disrupting chemicals (EDCs) ,Cancer Research ,Candidate gene ,Bisulfite sequencing ,Epigenesis, Genetic ,Rats, Sprague-Dawley ,stem cell pluripotency ,Estradiol ,Sprague Dawley rats ,The Cancer Genome Atlas (TCGA) ,Methylation ,Environmental exposure ,3. Good health ,DNA methylation ,Female ,Research Paper ,medicine.medical_specialty ,Pathway Analysis (IPA®) ,Air Pollutants, Occupational ,NimbleGen rat DNA methylation promoter array ,methylated-CpG island recovery assay (MIRA) ,Biology ,Andrology ,03 medical and health sciences ,Phenols ,SOX2 ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,Epigenetics ,Benzhydryl Compounds ,early-life reprogramming ,Molecular Biology ,epigenetics ,Prostatic Neoplasms ,Ingenuity® ,Environmental Exposure ,DNA Methylation ,Survival Analysis ,Rats ,Developmental origin of health and disease (DOHaD) ,030104 developmental biology ,Differentially methylated regions ,Endocrinology ,Genetic Loci ,CpG Islands - Abstract
Developmental exposure to endocrine-disrupting chemicals (EDCs), 17β-estradiol-3-benzoate (EB) and bisphenol A (BPA), increases susceptibility to prostate cancer (PCa) in rodent models. Here, we used the methylated-CpG island recovery assay (MIRA)-assisted genomic tiling and CpG island arrays to identify treatment-associated methylome changes in the postnatal day (PND)90 dorsal prostate tissues of Sprague-Dawley rats neonatally (PND1, 3, and 5) treated with 25 µg/pup or 2,500 µg EB/kg body weight (BW) or 0.1 µg BPA/pup or 10 µg BPA/kg BW. We identified 111 EB-associated and 86 BPA-associated genes, with 20 in common, that have significant differentially methylated regions. Pathway analysis revealed cancer as the top common disease pathway. Bisulfite sequencing validated the differential methylation patterns observed by array analysis in 15 identified candidate genes. The methylation status of 7 (Pitx3, Wnt10b, Paqr4, Sox2, Chst14, Tpd52, Creb3l4) of these 15 genes exhibited an inverse correlation with gene expression in tissue samples. Cell-based assays, using 5-aza-cytidine-treated normal (NbE-1) and cancerous (AIT) rat prostate cells, added evidence of DNA methylation-mediated gene expression of 6 genes (exception: Paqr4). Functional connectivity of these genes was linked to embryonic stem cell pluripotency. Furthermore, clustering analyses using the dataset from The Cancer Genome Atlas revealed that expression of this set of 7 genes was associated with recurrence-free survival of PCa patients. In conclusion, our study reveals that gene-specific promoter methylation changes, resulting from early-life EDC exposure in the rat, may serve as predictive epigenetic biomarkers of PCa recurrence, and raises the possibility that such exposure may impact human disease.
- Published
- 2016
3. Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids
- Author
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Kevin M. Tharp, Andreas Stahl, Kamran Atabai, Stephen Sakuma, Scott M. Turner, Yuk Yin Cheung, Ajay Chawla, Amin Khalifeh-Soltani, Yifu Qiu, and William McKleroy
- Subjects
Blood Glucose ,Blotting, Western ,Adipose tissue ,Mechanistic Target of Rapamycin Complex 2 ,Biology ,Cell Fractionation ,Real-Time Polymerase Chain Reaction ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,chemistry.chemical_compound ,Insulin resistance ,3T3-L1 Cells ,In Situ Nick-End Labeling ,medicine ,Animals ,Carbon Radioisotopes ,Obesity ,Phosphorylation ,adipocyte protein 2 ,Triglycerides ,DNA Primers ,Mice, Knockout ,chemistry.chemical_classification ,Analysis of Variance ,Microscopy, Confocal ,TOR Serine-Threonine Kinases ,Fatty Acids ,Fatty acid ,General Medicine ,Flow Cytometry ,Microarray Analysis ,Milk Proteins ,medicine.disease ,Dietary Fats ,Immunohistochemistry ,Oncogene Protein v-akt ,Oleic acid ,chemistry ,Biochemistry ,Multiprotein Complexes ,Antigens, Surface ,Body Composition ,biology.protein ,Phosphatidylinositol 3-Kinase ,MFGE8 ,Oleic Acid - Abstract
Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8(-/-)) mice are protected from diet-induced obesity, steatohepatitis and insulin resistance. Mechanistically, we found that Mfge8 coordinates fatty acid uptake through αvβ3 integrin- and αvβ5 integrin-dependent phosphorylation of Akt by phosphatidylinositide-3 kinase and mTOR complex 2, leading to translocation of Cd36 and Fatp1 from cytoplasmic vesicles to the cell surface. Collectively, our results imply a role for Mfge8 in regulating the absorption and storage of dietary fats, as well as in the development of obesity and its complications.
- Published
- 2014
4. Neonatal Exposure to Estradiol/Bisphenol A Alters Promoter Methylation and Expression of Nsbp1 and Hpcal1 Genes and Transcriptional Programs of Dnmt3a/b and Mbd2/4 in the RatProstate Gland Throughout Life
- Author
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Gail S. Prins, Lisa M. Morey, Wan Yee Tang, Lynn Birch, Shuk-Mei Ho, and Yuk Yin Cheung
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,DNMT3A Gene ,Gene Expression ,Nerve Tissue Proteins ,Biology ,Decitabine ,medicine.disease_cause ,DNA Methyltransferase 3A ,Rats, Sprague-Dawley ,Endocrinology ,Phenols ,Internal medicine ,medicine ,Animals ,DNA (Cytosine-5-)-Methyltransferases ,Epigenetics ,Benzhydryl Compounds ,RNA, Small Interfering ,Promoter Regions, Genetic ,DNA Primers ,Nucleosome binding ,Base Sequence ,Estradiol ,Calcium-Binding Proteins ,Prostate ,Methylation ,DNA Methylation ,Cancer-Oncogenes ,Rats ,DNA-Binding Proteins ,Animals, Newborn ,Estrogen ,DNA methylation ,Azacitidine ,HMGN Proteins ,Carcinogenesis ,Reprogramming - Abstract
Evidence supporting an early origin of prostate cancer is growing. We demonstrated previously that brief exposure of neonatal rats to estradiol or bisphenol A elevated their risk of developing precancerous lesions in the prostate upon androgen-supported treatment with estradiol as adults. Epigenetic reprogramming may be a mechanism underlying this inductive event in early life, because we observed overexpression of phosphodiesterase 4D variant 4 (Pde4d4) through induction of hypomethylation of its promoter. This epigenetic mark was invisible in early life (postnatal d 10), becoming apparent only after sexual maturation. Here, we asked whether other estrogen-reprogrammable epigenetic marks have similar or different patterns in gene methylation changes throughout life. We found that hypomethylation of the promoter of nucleosome binding protein-1 (Nsbp1), unlike Pde4d4, is an early and permanent epigenetic mark of neonatal exposure to estradiol/bisphenol A that persists throughout life, unaffected by events during adulthood. In contrast, hippocalcin-like 1 (Hpcal1) is a highly plastic epigenetic mark whose hypermethylation depends on both type of early-life exposure and adult-life events. Four of the eight genes involved in DNA methylation/demethylation showed early and persistent overexpression that was not a function of DNA methylation at their promoters, including genes encoding de novo DNA methyltransferases (Dnmt3a/b) and methyl-CpG binding domain proteins (Mbd2/4) that have demethylating activities. Their lifelong aberrant expression implicates them in early-life reprogramming and prostate carcinogenesis during adulthood. We speculate that the distinctly different fate of early-life epigenetic marks during adulthood reflects the complex nature of lifelong editing of early-life epigenetic reprogramming.
- Published
- 2012
5. Crystal Structure of a Hyperthermophilic Archaeal Acylphosphatase from Pyrococcus horikoshiiStructural Insights into Enzymatic Catalysis, Thermostability, and Dimerization
- Author
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Kam-Bo Wong, Sonia Y. Lam, Mark D. Allen, Yuk-Yin Cheung, Mark Bycroft, and Wai Kit Chu
- Subjects
Models, Molecular ,Stereochemistry ,Archaeal Proteins ,Molecular Sequence Data ,Crystallography, X-Ray ,Acylphosphatase ,medicine.disease_cause ,Biochemistry ,Catalysis ,Protein Structure, Secondary ,Substrate Specificity ,Enzyme catalysis ,Pyrococcus horikoshii ,Enzyme Stability ,Hydrolase ,medicine ,Animals ,Computer Simulation ,Amino Acid Sequence ,Escherichia coli ,Conserved Sequence ,Thermostability ,chemistry.chemical_classification ,Binding Sites ,biology ,Chemistry ,Thermophile ,Temperature ,biology.organism_classification ,Recombinant Proteins ,Acid Anhydride Hydrolases ,Enzyme Activation ,Crystallography ,Enzyme ,Thermodynamics ,Cattle ,Dimerization - Abstract
Acylphosphatases catalyze the hydrolysis of the carboxyl-phosphate bond in acyl phosphates. Although acylphosphatase-like sequences are found in all three domains of life, no structure of acylphosphatase has been reported for bacteria and archaea so far. Here, we report the characterization of enzymatic activities and crystal structure of an archaeal acylphosphatase. A putative acylphosphatase gene (PhAcP) was cloned from the genomic DNA of Pyrococcus horikoshii and was expressed in Escherichia coli. Enzymatic parameters of the recombinant PhAcP were measured using benzoyl phosphate as the substrate. Our data suggest that, while PhAcP is less efficient than other mammalian homologues at 25 degrees C, the thermophilic enzyme is fully active at the optimal growth temperature (98 degrees C) of P. horikoshii. PhAcP is extremely stable; its apparent melting temperature was 111.5 degrees C and free energy of unfolding at 25 degrees C was 54 kJ mol(-)(1). The 1.5 A crystal structure of PhAcP adopts an alpha/beta sandwich fold that is common to other acylphosphatases. PhAcP forms a dimer in the crystal structure via antiparallel association of strand 4. Structural comparison to mesophilic acylphosphatases reveals significant differences in the conformation of the L5 loop connecting strands 4 and 5. The extreme thermostability of PhAcP can be attributed to an extensive ion-pair network consisting of 13 charge residues on the beta sheet of the protein. The reduced catalytic efficiency of PhAcP at 25 degrees C may be due to a less flexible active-site residue, Arg20, which forms a salt bridge to the C-terminal carboxyl group. New insights into catalysis were gained by docking acetyl phosphate to the active site of PhAcP.
- Published
- 2005
6. Mfge8 Prevents Airway Constriction In Asthma By Opposing The Effect Of IL-13 On Airway Smooth Muscle Calcium Sensitivity
- Author
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Kamran Atabai, Yuk Yin Cheung, Jae-Woo Lee, Stephen Sakuma, Makoto Kudo, William McKleroy, and Katherine Huang
- Subjects
medicine.medical_specialty ,business.industry ,Airway smooth muscle ,medicine.disease ,Endocrinology ,Internal medicine ,Interleukin 13 ,medicine ,Calcium sensitivity ,Bronchoconstriction ,MFGE8 ,medicine.symptom ,business ,Asthma - Published
- 2012
7. Glucose-6-phosphatase-β, implicated in a congenital neutropenia syndrome, is essential for macrophage energy homeostasis and functionality
- Author
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Hyun Sik Jun, Yuk Yin Cheung, Young Mok Lee, Brian C. Mansfield, and Janice Y. Chou
- Subjects
Neutropenia ,Immunology ,Blotting, Western ,G6PC3 ,Glucose-6-Phosphate ,Inflammation ,Apoptosis ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Energy homeostasis ,Immunoenzyme Techniques ,Mice ,Phagocytes, Granulocytes, and Myelopoiesis ,Phagocytosis ,Pregnancy ,Calcium flux ,medicine ,Animals ,Congenital Bone Marrow Failure Syndromes ,Homeostasis ,RNA, Messenger ,Congenital Neutropenia ,Cell Proliferation ,Respiratory Burst ,Mice, Knockout ,Glucose Transporter Type 1 ,NADPH oxidase ,biology ,Glucose Transporter Type 3 ,Chemotaxis ,Macrophages ,NADPH Oxidases ,Cell Biology ,Hematology ,Syndrome ,medicine.disease ,Mice, Inbred C57BL ,Glucose ,biology.protein ,Glucose-6-Phosphatase ,Cytokines ,Calcium ,Female ,medicine.symptom ,Glucose 6-phosphatase ,Signal Transduction - Abstract
Glucose-6-phosphatase-β (G6Pase-β or G6PC3) deficiency, also known as severe congenital neutropenia syndrome 4, is characterized not only by neutropenia but also by impaired neutrophil energy homeostasis and functionality. We now show the syndrome is also associated with macrophage dysfunction, with murine G6pc3−/− macrophages having impairments in their respiratory burst, chemotaxis, calcium flux, and phagocytic activities. Consistent with a glucose-6-phosphate (G6P) metabolism deficiency, G6pc3−/− macrophages also have a lower glucose uptake and lower levels of G6P, lactate, and ATP than wild-type macrophages. Furthermore, the expression of NADPH oxidase subunits and membrane translocation of p47phox are down-regulated, and G6pc3−/− macrophages exhibit repressed trafficking in vivo both during an inflammatory response and in pregnancy. During pregnancy, the absence of G6Pase-β activity also leads to impaired energy homeostasis in the uterus and reduced fertility of G6pc3−/− mothers. Together these results show that immune deficiencies in this congenital neutropenia syndrome extend beyond neutrophil dysfunction.
- Published
- 2012
8. Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-β–deficient neutrophils in a congenital neutropenia syndrome
- Author
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Janice Y. Chou, Yuk Yin Cheung, Philip M. Murphy, Suk See De Ravin, David H. McDermott, Hyun Sik Jun, Brian C. Mansfield, and Young Mok Lee
- Subjects
Male ,Cytoplasm ,Neutropenia ,Adolescent ,Neutrophils ,Glucose uptake ,Immunology ,G6PC3 ,Apoptosis ,Pentose phosphate pathway ,Glycogen Storage Disease Type I ,Endoplasmic Reticulum ,Biochemistry ,Phagocytes, Granulocytes, and Myelopoiesis ,Mice ,Adenosine Triphosphate ,Stress, Physiological ,medicine ,Animals ,Humans ,Lactic Acid ,Annexin A5 ,Child ,Mice, Knockout ,Glucose Transporter Type 1 ,NADPH oxidase ,biology ,Caspase 3 ,Endoplasmic reticulum ,NADPH Oxidases ,Cell Biology ,Hematology ,Syndrome ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,Glucose ,biology.protein ,Unfolded protein response ,Glucose-6-Phosphatase ,Female ,Glucose 6-phosphatase - Abstract
G6PC3 deficiency, characterized by neutropenia and neutrophil dysfunction, is caused by deficiencies in the endoplasmic reticulum (ER) enzyme glucose-6-phosphatase-β (G6Pase-β or G6PC3) that converts glucose-6-phosphate (G6P) into glucose, the primary energy source of neutrophils. Enhanced neutrophil ER stress and apoptosis underlie neutropenia in G6PC3 deficiency, but the exact functional role of G6Pase-β in neutrophils remains unknown. We hypothesized that the ER recycles G6Pase-β–generated glucose to the cytoplasm, thus regulating the amount of available cytoplasmic glucose/G6P in neutrophils. Accordingly, a G6Pase-β deficiency would impair glycolysis and hexose monophosphate shunt activities leading to reductions in lactate production, adenosine-5′-triphosphate (ATP) production, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Using annexin V–depleted neutrophils, we show that glucose transporter-1 translocation is impaired in neutrophils from G6pc3−/− mice and G6PC3-deficient patients along with impaired glucose uptake in G6pc3−/− neutrophils. Moreover, levels of G6P, lactate, and ATP are markedly lower in murine and human G6PC3-deficient neutrophils, compared with their respective controls. In parallel, the expression of NADPH oxidase subunits and membrane translocation of p47phox are down-regulated in murine and human G6PC3-deficient neutrophils. The results establish that in nonapoptotic neutrophils, G6Pase-β is essential for normal energy homeostasis. A G6Pase-β deficiency prevents recycling of ER glucose to the cytoplasm, leading to neutrophil dysfunction.
- Published
- 2010
9. Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta
- Author
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So Youn Kim, Robert A. Ruef, Chi-Jiunn Pan, Eric J. Lee, Yuk Yin Cheung, Hyun-Sik Jun, Brian C. Mansfield, Wai Han Yiu, Heiner Westphal, and Janice Y. Chou
- Subjects
Blood Glucose ,medicine.medical_specialty ,G6PC ,Neutropenia ,Neutrophils ,G6PC3 ,Glucose-6-Phosphate ,Peritonitis ,chemistry.chemical_compound ,Mice ,Internal medicine ,Calcium flux ,medicine ,Glucose homeostasis ,Animals ,Homeostasis ,Genetic Predisposition to Disease ,biology ,General Medicine ,Bacterial Infections ,medicine.disease ,Respiratory burst ,Hematopoiesis ,Disease Models, Animal ,Protein Subunits ,Endocrinology ,Glucose 6-phosphate ,chemistry ,Immunology ,biology.protein ,Glucose-6-Phosphatase ,Glucose 6-phosphatase ,Research Article - Abstract
Neutropenia and neutrophil dysfunction are common in many diseases, although their etiology is often unclear. Previous views held that there was a single ER enzyme, glucose-6-phosphatase-alpha (G6Pase-alpha), whose activity--limited to the liver, kidney, and intestine--was solely responsible for the final stages of gluconeogenesis and glycogenolysis, in which glucose-6-phosphate (G6P) is hydrolyzed to glucose for release to the blood. Recently, we characterized a second G6Pase activity, that of G6Pase-beta (also known as G6PC), which is also capable of hydrolyzing G6P to glucose but is ubiquitously expressed and not implicated in interprandial blood glucose homeostasis. We now report that the absence of G6Pase-beta led to neutropenia; defects in neutrophil respiratory burst, chemotaxis, and calcium flux; and increased susceptibility to bacterial infection. Consistent with this, G6Pase-beta-deficient (G6pc3-/-) mice with experimental peritonitis exhibited increased expression of the glucose-regulated proteins upregulated during ER stress in their neutrophils and bone marrow, and the G6pc3-/- neutrophils exhibited an enhanced rate of apoptosis. Our results define a molecular pathway to neutropenia and neutrophil dysfunction of previously unknown etiology, providing a potential model for the treatment of these conditions.
- Published
- 2006
10. Brain contains a functional glucose-6-phosphatase complex capable of endogenous glucose production
- Author
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Janice Yang Chou, Brian C. Mansfield, Abhijit Ghosh, and Yuk Yin Cheung
- Subjects
Snf3 ,Glycogenolysis ,Monosaccharide Transport Proteins ,Endogeny ,macromolecular substances ,Biology ,Biochemistry ,Antiporters ,chemistry.chemical_compound ,Mice ,Animals ,Molecular Biology ,Glycogen ,Phosphotransferases ,Glucose transporter ,Brain ,Transporter ,Cell Biology ,Phosphoric Monoester Hydrolases ,carbohydrates (lipids) ,Glucose ,Gluconeogenesis ,chemistry ,Astrocytes ,COS Cells ,biology.protein ,Glucose-6-Phosphatase ,lipids (amino acids, peptides, and proteins) ,Glucose 6-phosphatase - Abstract
Glucose is absolutely essential for the survival and function of the brain. In our current understanding, there is no endogenous glucose production in the brain, and it is totally dependent upon blood glucose. This glucose is generated between meals by the hydrolysis of glucose-6-phosphate (Glc-6-P) in the liver and the kidney. Recently, we reported a ubiquitously expressed Glc-6-P hydrolase, glucose-6-phosphatase-beta (Glc-6-Pase-beta), that can couple with the Glc-6-P transporter to hydrolyze Glc-6-P to glucose in the terminal stages of glycogenolysis and gluconeogenesis. Here we show that astrocytes, the main reservoir of brain glycogen, express both the Glc-6-Pase-beta and Glc-6-P transporter activities and that these activities can couple to form an active Glc-6-Pase complex, suggesting that astrocytes may provide an endogenous source of brain glucose.
- Published
- 2005
11. Crystallization and preliminary crystallographic analysis of an acylphosphatase from the hyperthermophilic archaeon Pyrococcus horikoshii
- Author
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Kam-Bo Wong, Mark D. Allen, Yuk-Yin Cheung, and Mark Bycroft
- Subjects
biology ,Sodium formate ,Molecular Sequence Data ,General Medicine ,Phosphate ,biology.organism_classification ,Acylphosphatase ,Crystallography, X-Ray ,law.invention ,Acid Anhydride Hydrolases ,chemistry.chemical_compound ,Hydrolysis ,Amyloid disease ,Crystallography ,Pyrococcus horikoshii ,chemistry ,Structural Biology ,law ,Carbamoyl phosphate ,Animals ,Amino Acid Sequence ,Crystallization ,Sequence Alignment - Abstract
Acylphosphatases catalyse the hydrolysis of the carboxyl phosphate bond in metabolites such as acetyl phosphate, 1,3-bisphosphoglycerate, succinoyl phosphate and carbamoyl phosphate. In this study, acylphosphatase (91 residues) from the hyperthermophilic archaeon Pyrococcus horikoshii has been cloned, overexpressed, purified and crystallized using the sitting-drop vapour-diffusion method using sodium formate as a precipitant at 289 K. The crystals belong to space group P3(2)21, with unit-cell parameters a = b = 85.65, c = 75.51 A. The asymmetric unit contains two molecules of acylphosphatase, with a corresponding crystal volume per protein weight of 3.9 A Da(-1) and a solvent content of 68.6%. A data set diffracting to 1.6 A resolution was collected from a single crystal at 100 K.
- Published
- 2004
12. Maternal Exposure to Polycyclic Aromatic Hydrocarbons and 5'-CpG Methylation of Interferon-γ in Cord White Blood Cells.
- Author
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Wan-yee Tang, Levin, Linda, Talaska, Glenn, Yuk Yin Cheung, Herbstman, Julie, Tang, Deliang, Miller, Rachel L., Perera, Frederica, and Shuk-Mei Ho
- Subjects
DNA analysis ,ASTHMA ,BIOPHYSICS ,CELL culture ,CHI-squared test ,STATISTICAL correlation ,CORD blood ,GENE expression ,GENES ,HYDROCARBONS ,INTERFERONS ,INTERLEUKINS ,LEUCOCYTES ,RESEARCH methodology ,METHYLATION ,MOTHERS ,POLYMERASE chain reaction ,REGRESSION analysis ,RESEARCH funding ,REVERSE transcriptase polymerase chain reaction ,DATA analysis software ,STATISTICAL models ,DESCRIPTIVE statistics ,SEQUENCE analysis ,PREGNANCY - Abstract
Background: Maternal factors are implicated in the onset of childhood asthma. Differentiation of naïve CD4+ T lymphocytes into pro-allergic T-helper 2 cells induces interleukin (IL)4 expression and inhibits interferon (IFN)γ expression accompanied by concordant methylation changes in the promoters of these genes. However, it has yet to be established whether maternal exposure to polycyclic aromatic hydrocarbons (PAHs) can alter these gene promoters epigenetically during fetal development. Objectives: In this study we sought to elucidate the relationship between maternal PAH exposure and promoter methylation status of IFNγ and IL4. Methods: We assessed the effects of benzo[a]pyrene (BaP), a representative airborne PAH, on the methylation status of the IFNγ and IL4 promoters in Jurkat cells and two lung adenocarcinoma cell lines, and on gene expression. In addition, we evaluated methylation status of the IFNγ promoter in cord white blood cells from 53 participants in the Columbia Center for Children's Environmental Health cohort. Maternal PAH exposure was estimated by personal air monitoring during pregnancy. Results: In vitro exposure of the cell models to low, noncytotoxic doses (0.1 and 1 nM) of BaP elicited increased promoter hypermethylation and reduced expression of IFNγ, but not IL4. IFNγ promoter methylation in cord white blood cells was associated with maternal PAH exposure in the cohort study subsample. Conclusion: Consistent with the results for the cell lines, maternal exposure to PAHs was associated with hypermethylation of IFNγ in cord blood DNA from cohort children. These findings support a potential role of epigenetics in fetal reprogramming by PAH-induced environmental diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
13. Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase--β.
- Author
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Yuk Yin Cheung, So Youn Kim, Wai Han Yiu, Chi-Jiunn Pan, Hyun-Sik Jun, Ruef, Robert A., Lee, Eric J., Westphal, Heiner, Mansfield, Brian C., and Chou, Janice Y.
- Subjects
- *
NEUTROPENIA , *GRANULOCYTOPENIA , *ETIOLOGY of diseases , *NEUTROPHILS , *GLUCOSE-6-phosphatase , *BACTERIAL diseases - Abstract
Neutropenia and neutrophil dysfunction are common in many diseases, although their etiology is often unclear. Previous views held that there was a single ER enzyme, glucose-6-phosphatase-α (G6Pase-α), whose activity — limited to the liver, kidney, and intestine — was solely responsible for the final stages of gluconeogenesis and glycogenolysis, in which glucose-6-phosphate (G6P) is hydrolyzed to glucose for release to the blood. Recently, we characterized a second G6Pase activity, that of G6Pase-β (also known as G6PC), which is also capable of hydrolyzing G6P to glucose but is ubiquitously expressed and not implicated in interprandial blood glucose homeostasis. We now report that the absence of G6Pase-β led to neutropenia; defects in neutrophil respiratory burst, chemotaxis, and calcium flux; and increased susceptibility to bacterial infection. Consistent with this, G6Pase-β-deficient (G6pc3-/-) mice with experimental peritonitis exhibited increased expression of the glucose-regulated proteins upregulated during ER stress in their neutrophils and bone marrow, and the G6pc3-/- neutrophils exhibited an enhanced rate of apoptosis. Our results define a molecular pathway to neutropenia and neutrophil dysfunction of previously unknown etiology, providing a potential model for the treatment of these conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
14. Brain Contains a Functional Glucose-6-Phosphatase Complex Capable of Endogenous Glucose Production.
- Author
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Ghosh, Abhijit, Yuk Yin Cheung, Mansfield, Brian C., and Yang Chou, Janice
- Subjects
- *
GLUCOSE-6-phosphatase , *PHOSPHATASES , *GLUCOSE , *BRAIN chemistry , *BRAIN , *BIOCHEMISTRY - Abstract
Glucose is absolutely essential for the survival and function of the brain. In our current understanding, there is no endogenous glucose production in the brain, and it is totally dependent upon blood glucose. This glucose is generated between meals by the hydrolysis of glucose-6-phosphate (Glc-6-P) in the liver and the kidney. Recently, we reported a ubiquitously expressed Glc-6-P hydrolase, glucose-6-phosphatase-β (Glc-6-Paseβ), that can couple with the Glc-6-P transporter to hydrolyze Glc-6-P to glucose in the terminal stages of glycogenolysis and gluconeogenesis. Here we show that astrocytes, the main reservoir of brain glycogen, express both the Glc-6-Pase-β and Glc-6-P transporter activities and that these activities can couple to form an active Glc-6-Pase complex, suggesting that astrocytes may provide an endogenous source of brain glucose. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
15. Crystallization and preliminary crystallographic analysis of an acylphosphatase from the hyperthermophilic archaeon Pyrococcus horikoshii.
- Author
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Yuk-Yin Cheung, Allen, Mark D., Bycroft, Mark, and Kam-Bo Wong
- Subjects
- *
PHOSPHATASES , *CLONING , *CRYSTALLIZATION , *CHEMICAL purification , *RESEARCH - Abstract
Discusses research on the cloning, overexpression, purification and crystallization of acylphosphatase from the hyperthermophilic archaeon Pyrococcus horikoshii. Information on acylphosphatase; Crystallization and data processing; Obtainment of a molecular-replacement solution.
- Published
- 2004
- Full Text
- View/download PDF
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