Nutrition & Food Science
Permanent URI for this communityhttp://hdl.handle.net/1903/2267
null
Browse
5 results
Search Results
Item HOW SELENIUM MODIFIES CROSS-TALK BETWEEN THE PIKK FAMILY AND INSIGHTS ON THE REGULATION OF DNA-PKcs(2009) Rocourt, Caroline; Cheng, Wen-Hsing; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)We recently found that ATM is required for a selenium-induced senescence response in non-cancerous cells. We hypothesize the selenium-induced DNA damage response modifies ATM and DNA-PKcs cross-talk. Phospho-specific antibodies against ATM and DNA-PKcs were used to follow the phosphorylation events after selenium treatment in normal human cells and two human cancer cell lines. Results from immunofluorescence analysis showed that selenium treatment induces hyperphosphorylation of DNA-PKcs at T2647 and S2056 in non-cancerous MRC-5 cells but not in U-2 OS cancer cells. Further studies in MRC-5 cells treated with an ATM kinase inhibitor, KU 55933, showed attenuation of the selenium-induced DNA-PKcs phosphorylation at both foci, whereas pre-treatment with a DNA-PKcs kinase inhibitor, NU 7026, does not prevent ATM phosphorylation at S1981, an event leading to ATM pathway activation. These results give evidence that DNA-PKcs and ATM have a cooperative role in the DNA damage response pathway.Item High Sucrose, Fructose, and Glucose Diets and Glucocorticoid Dysregulation in Rats(2009) London, Edra; Castonguay, Thomas W; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Approximately two-thirds of U.S. adults are overweight or obese and the prevalence of overweight in children has tripled since 1980. Intake of added sugars has also increased. The etiology of obesity remains unclear and the role of glucocorticoids in obesity is one area of ambiguity. The enzyme 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1) interconverts active and inactive glucocorticoid, thereby regulating intracellular glucocorticoids. Dysregulation of 11beta-HSD-1 in liver and adipose is characteristic of human and animal models of obesity. Hexose-6-phosphate dehydrogenase (H6PDH) is colocalized with 11beta-HSD-1 and determines the set point for 11beta-HSD-1 oxidoreductase activity. In a long-term (10 wk) study, rats given ad libitum access to 16% sucrose solution, chow, and water were fatter than controls, had increased 11beta-HSD-1 mRNA in adipose, suppressed 11beta-HSD-1 mRNA in liver, and increased H6PDH mRNA in both tissues. The primary research questions were as follows: Can high sugar diets induce glucocorticoid dysregulation in the absence of excess adiposity? Does sugar type matter? Energy intake, weight gain, and parameters of lipid and carbohydrate metabolism were measured. Rats were randomly assigned to either ad libitum access to chow and water only (control), or in addition to ad libitum access to either 16% sucrose, fructose, or glucose solution (n=16/gp). After 24h and 1 wk, eight rats per group were randomly selected for sacrifice. Daily caloric intakes among sugar-fed groups did not differ and were higher than the mean intake of the control group. Within 24h, fructose induced increased 11beta-HSD-1 message in mesenteric adipose and liver. Plasma TG and insulin were acutely increased in groups with fructose-containing diets only. All high sugar diets induced suppressed hepatic 11beta-HSD-1 mRNA and protein after 1 wk. Upregulation of H6PDH mRNA observed in response to long-term high sucrose diets may result from increased adiposity and not solely diet. High sugar diets, irrespective of sugar type, initiate glucocorticoid dysregulation in the absence of phenotypic changes associated with obesity. Sucrose, fructose, and glucose have distinct metabolic and endocrine responses. Fructose has the unique ability to induce glucocorticoid dysregulation in liver and adipose in 24h.Item Modulation of Human Tumor Suppressor Genes, Gadd45, p53 and p38 MAPK by Zinc Status in Normal Human Bronchial Epithelial Cells(2007-05-08) Shih, Sheung-Mei; Lei, David K.Y.; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The effect of zinc status on the cell signaling transduction of tumor suppressor genes, Growth Arrest and DNA Damage inducible gene (Gadd45), p53, and p38 Mitogen Activated Protein Kinase (MAPK) were examined in Normal Human Bronchial Epithelial (NHBE) cells. Cells were cultured for one passage in different concentrations of zinc: < 0.4 μM (ZD, zinc-deficient); 4 μM (ZN, zinc normal) as normal zinc level found in most culture medium; 16 μM (ZA, zinc adequate) represented normal human plasma zinc level; and 32 μM (ZS, zinc supplementation) represented the optimal plasma zinc attainable by oral supplementation. Cell growth inhibition, up-regulation of Gadd45, p53 and p38 MAPK mRNA and protein expressions, and blockage of G2/M cell cycle progression were observed in ZS cells. The siRNA-mediated knocking down of Gadd45 was found to alleviate G2/M blockage partially in ZS cells, which indicated that the blockage is partially Gadd45 dependent. In ZS cells, the enhanced phosphorylation of p38 MAPK and p53 were abrogated after suppressing Gadd45 by siRNA, implicating that the enhanced phosphorylation of p53 and p38 MAPK were Gadd45 dependent. By using p53 transactivation inhibitor Pifithrin, the upregulated Gadd45 protein, the enhanced Gadd45 promoter activity, and the reduced level of CDK1/Cyclin B1 complex were all restored back to normal levels in ZS cell, implying that these ZS induced changes were p53 dependent. Furthermore, the ZS induced upregulation of Gadd45 expression, displacement of CDC25B from nucleus to cytoplasm, reduction of CDK1/Cyclin B1 complex level, enhancement of the activation and phosphorylation of p53, and delay of G2/M cell cycle progression were normalized by p38 MAPK dominant negative and protein inhibitor SB202190. Thus, the ZS induced changes were dependent on the activation of p38 MAPK. Our data support the involvement of a positive Gadd45, p53 and p38 MAPK feedback loop in response to stress induced by zinc supplementation. These findings demonstrate the importance of p38 MAPK and p53 in the regulation of G2/M cell cycle progression in response to the stress induced by high zinc via Gadd45 and cell cycle checkpoint regulatory proteins, including CDK1, Cyclin B1 and CDC25B.Item Modulation of p21 Human Tumor Suppressor Gene Expression By Zinc Status In Human Hepatoblastoma And Normal Human Bronchial Epithelial Cells(2007-05-01) WONG, Hon-Kit; Lei, David K.Y.; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The transcriptional regulation of p21 gene in both human hepatoblastoma (HepG2) cells and normal human bronchial epithelial (NHBE) cells in response to different zinc status has been examined. In both zinc deficient (ZD) and zinc marginal deficient (ZD0.4) HepG2 cells, the p21 mRNA and nuclear protein levels as well as p21 promoter activity were repressed as compared to that of zinc normal (ZN) control cells. However, they were not altered in zinc adequate (ZA) and zinc supplement (ZS) cells as compared to ZN cells. Moreover, transfection of a construct consisted of a constitutive promoter fused with a full length p21 coding sequence in ZD cells, normalized p21 protein expression to that of the ZN cells, but failed to correct cell growth reduction. Similar transfection in ZN cells overexpressed p21 and repressed cell growth. Thus, the present data indicate that in zinc-deficient HepG2 cells, the p21 transcriptional process is depressed. However, depressed p21 transcriptional process is not responsible for repressed cell growth in zinc-deficient HepG2 cells. In NHBE cells, the nuclear p21 protein level and mRNA abundance as well as promoter activity in ZS cells, but not in ZD cells, were markedly elevated to almost 2-fold when compared to ZN control cells. G2/M blockage in ZS cells was coupled with enhanced p21 gene expression. In ZS cells, the abrogation of p21 protein induction by the transfection of p21 siRNA was shown to alleviate the G2/M blockage. A similar gene knock-down approach was used to establish if the p21 upregulation in ZS cells was p53 dependent. Abolishment of the increase in p53 protein in ZS cells with transfection of p53 siRNA normalized the elevated p21 protein to a similar level as in ZN control cells, which demonstrated that the p21 induction is p53-dependent. Furthermore, the normalization of p53 protein by siRNA in ZS cells alleviated cell growth depression and G2/M blockage, which demonstrated that p53 was involved in the high zinc status induced G2/M blockage and growth depression. Thus, high zinc status in NHBE cells upregulated p53 expression which in turn elevated p21 that eventually induced G2/M blockage.Item THE EFFECTS OF OBESITY ON PLASMA LEVELS OF OMENTIN, A DEPOT-SPECIFIC ADIPOCYTOKINE(2004-08-27) de Souza Batista, Celia Maria; Kantor, Mark; McLenithan, John; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Obesity is a chronic pathological condition and a risk factor for diabetes and cardiovascular disease. It has been demonstrated that adipose tissue functions not only as a fat storage depot but also as an endocrine organ. Omentin is a protein expressed and secreted in adipose tissue that increases insulin-stimulated glucose transport. To further elucidate omentin's physiological function, its levels were measured by quantitative western blotting in plasma from 44 healthy nondiabetic volunteers (22 women, 22 men). Participants were organized into sibling pairs based on discordant BMI (3-12 Kg/m2). Lean subjects had significantly higher omentin levels than obese/overweight subjects (independent of sex), and significantly higher omentin levels were detected in women compared to men. Omentin levels were inversely correlated with BMI and positively correlated with HDL levels. These data suggest that omentin may play a physiological role in the pathogenesis of obesity-dependent insulin resistance.