Nutrition & Food Science
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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 Why do African Americans have higher serum ferritin than European Americans, despite lower hemoglobin?(2006-07-12) Pan, Yang; Jackson, Robert T.; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Blacks have been consistently observed to have higher serum ferritin (SF) concentrations than whites; however, few studies have attempted to explore why this difference exists. 3,554 non-Hispanic white (NHW) and non-Hispanic black (NHB) male subjects, aged 20-65 years, were selected from the third National Health and Nutrition Examination Survey (NHANES III) to determine the possible factors that may contribute to the observed black-white SF difference. Results of multiple regression analyses showed that age, body mass index (BMI), % energy from carbohydrate and fat, calcium intake, serum total protein, serum α-carotene, mean cell volume (MCV), iron binding capacity (TIBC) and γ glutamyl transferase (GGT) were significantly associated with SF concentration. When the final regression model was run after excluding subjects with abnormal serum total protein, TIBC and GGT levels, the SF difference dropped to 3.95µg/L (initial difference=37.06µg/L) between NHWs and NHBs. The results suggest that the noted black-white SF difference is a result of factors including overall nutrition and health, iron status and hepatic well-being. Higher SF, low Hb and reduced TIBC level observed in blacks are consistent with the definition of anemia of chronic disease (ACD). Future investigations are needed to confirm the role of ACD in the black-white SF difference. We also examined different sub-populations to investigate whether the likelihood and magnitude of SF elevation in regard to acute inflammation and hepatitis C are different between NHBs and NHWs by using logistic regression analyses. Compared to NHWs, NHBs had a 2.239-fold (95% CI, 1.333 to 3.760) greater risk to have elevated SF in regard to acute inflammation, and had significantly higher odds ratios of having elevated SF per unit change in C-reactive protein (CRP), white blood cell count (WBC), serum albumin, lymphocyte and platelet count. However, no significant results were found for hepatitis C. The results indicated that NHWs and NHBs had different patterns of iron accumulation in regard to acute inflammation. Further elucidation is needed about how ferritin regulation is perturbed in diseases, and whether increased stored iron plays a role in different clinical outcomes and drug response. Adequately powered studies are needed to further investigate the relationship between stored iron and hepatitis C host response.Item DOSE RANGING STUDY OF LUTEIN SUPPLEMENTATION IN ELDERLY WITH AND WITHOUT AGE RELATED MACULAR DEGENERATION(2004-09-15) Moura, Fabiana Fonseca; Khachik, Frederick; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Age-related macular degeneration (AMD) is the leading cause of blindness among people over the age of 65. Epidemiological studies have indicated that people with a high intake of two dietary carotenoids, lutein and zeaxanthin that accumulate in the human macula, are at a reduced risk of AMD. Possible role of lutein and zeaxanthin in the prevention of AMD has been attributed to their antioxidant function and their ability to act as optical filters. The objectives of this study were to investigate the association between three doses of orally ingested lutein supplements and serum levels of this carotenoid in elderly with and without AMD; to evaluate the possible interaction between supplemental lutein and other dietary carotenoids, retinol, and tocopherol; to correlate the serum levels of lutein with the total macular pigment optical density (MPOD). Forty-five subjects over the age of 60 were divided into 3 groups: subjects without AMD and subjects with middle and end stage of AMD. Subjects in each group were randomized to receive one of the three doses of 2.5, 5, and 10 mg/day of lutein (containing 5% zeaxanthin) for 6 months. Subjects were followed up for 6 months. Carotenoids and their metabolites in the serum of subjects were analyzed by HPLC at weeks 0, 1, 4, 12, 26, 38, and 52. The MPOD of subjects was measured by Heterochromatic Flicker Photometry (HCFP). The data were analyzed using analysis of variance and covariance with repeated measurements (SAS, version 8.2). The mean serum concentrations of lutein in all subjects increased with supplementation. Subjects receiving 10 mg/day of lutein had a 3-4 fold increase in their serum levels of lutein, while those receiving 2.5 and 5 mg/day dose had approximately 2 fold increase. In conclusion, the serum concentration of lutein appears to be dose dependent and the presence or the absence of AMD does not interfere with the serum levels of this carotenoid. Supplemental lutein does not interact with other dietary carotenoids, retinol, and tocopherol. The results from MPOD measurements by HCFP were inconsistent and could not be used to reach any conclusion with regard to MPOD changes.