Publications by authors named "Jesse Bertinato"

28 Publications

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Iodine Status of Canadian Children, Adolescents and Women of Childbearing Age.

J Nutr 2021 Jul 27. Epub 2021 Jul 27.

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Background: Adequate iodine intake is important for children and women of childbearing age because iodine is vital for fetal brain development and early life.

Objective: Iodine status of children (n = 1875), adolescents (n = 557) and women of childbearing age (n = 567) was assessed using urinary iodine concentrations (UIC) from duplicate spot samples collected in the Canadian Health Measures Survey, cycle 5 (2016 - 2017).

Methods: Daily iodine intakes were estimated from urinary iodine and creatinine concentrations using a formula based on iodine absorption and predicted 24-h creatinine excretion. Usual UIC and iodine intakes, adjusted for within-person variation, were estimated using the National Cancer Institute method. Iodine status was assessed by (1) comparing median UIC with WHO/UNICEF/ICCIDD reference ranges and (2) estimating the prevalence of inadequate and excessive intakes using the Estimated Average Requirement (EAR) and Tolerable Upper Intake Level (UL) cut-point method, respectively.

Results: Median UIC for males or females 6 - 11 y or 12 - 19 y were ≥100 µg/L, the lower cut-off for adequate intakes. For women 20 - 39 y, median UIC (95% CI) of an unadjusted sample was 81 µg/L (67, 95) and for usual UIC 108 µg/L (84, 131). Percentage of children 3 y with iodine intakes ≥ EAR was 82% (75, 89). The corresponding estimates for males 4 - 8 y, 9 - 13 y and 14 - 18 y were 93% (88, 97), 91% (87, 96) and 84% (76, 91), respectively. Estimates for females were 4 - 8 y 86% (83, 89), 9 - 13 y 87% (80, 95), 14 - 18 y 68% (55, 80) and 19 - 39 y 68% (59, 76). For all sex-age groups, 91 - 100% had iodine intakes ≤ UL.

Conclusions: Iodine intakes may be insufficient for some women of childbearing age. Public health policies and programs should continue to recommend that all women who could become pregnant, or women who are pregnant or breastfeeding, take a daily multivitamin-mineral supplement containing iodine.
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http://dx.doi.org/10.1093/jn/nxab268DOI Listing
July 2021

Iodine nutrition: Disorders, monitoring and policies.

Authors:
Jesse Bertinato

Adv Food Nutr Res 2021 24;96:365-415. Epub 2021 Feb 24.

Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada. Electronic address:

Iodine is an essential mineral nutrient and an integral component of thyroid hormones. Iodine deficiency is typically associated with goiter, but can have more serious health implications. Adequate iodine status is important for normal brain development. Iodine deficiency in utero or in early life can cause severe neurological and cognitive impairment. Over the last three decades, global efforts have reduced the prevalence of iodine deficiency disorders (IDD) in many areas of the world with implementation of nutrition policies and programs such as "salt" iodization. However, in a number of areas iodine deficiency is still widespread. Iodine deficiency in remote regions with high poverty will be more difficult to eradicate. Efforts to eliminate IDD in affected areas and sustaining successful iodine programs will be a priority given the substantial public health and economic benefits. A key component will be periodic monitoring of population iodine status to ensure sufficient intakes and the absence of excessive intakes. Median urinary iodine concentration (UIC), a validated biomarker for assessing population iodine status, will facilitate monitoring. Research validating "usual" UIC for use in combination with the Estimated Average Requirement cut-point method will expand its utility and allow accurate determination of the prevalence of inadequate intakes in populations. Further research on the development of biomarkers for assessment of individual iodine status for routine patient care will be important.
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http://dx.doi.org/10.1016/bs.afnr.2021.01.004DOI Listing
February 2021

Calcium exacerbates the inhibitory effects of phytic acid on zinc bioavailability in rats.

J Trace Elem Med Biol 2020 Dec 8;62:126643. Epub 2020 Sep 8.

Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada. Electronic address:

Background: Complementary feeding of breastfed infants with foods high in bioavailable zinc (Zn) can help meet physiological requirements for Zn. Some infant cereals contain high concentrations of phytic acid (PA) and calcium (Ca) that may reduce absorbable Zn.

Objectives: This study measured PA, Zn and Ca concentrations in selected infant cereals sold in Canada and investigated the effects of dietary PA and Ca at concentrations present in infant cereals on Zn bioavailability in rats.

Methods And Results: Male Sprague-Dawley rats (36-day old) were fed a control diet containing normal Zn (29.1 mg/kg) and Ca (4.95 g/kg) or six test diets (n = 12/diet group). Test diets were low in Zn (8.91-9.74 mg/kg) and contained low (2.16-2.17 g/kg), normal (5.00-5.11 g/kg) or high (14.6-14.9 g/kg) Ca without or with added PA (8 g/kg). After 2 weeks, rats were killed and Zn status of the rats was assessed. PA, Zn and Ca concentrations in infant cereals (n = 20) differed widely. PA concentrations ranged from undetectable to 16.0 g/kg. Zn and Ca concentrations ranged from 7.0-29.1 mg/kg and 0.8-13.4 g/kg, respectively. The [PA]/[Zn] and [PA × Ca]/[Zn] molar ratios in infants cereals with detectable PA (16 of 20 cereals) ranged from 22-75 and 0.9-14.9 mol/kg, respectively, predicting low Zn bioavailability. Body weight, body composition (lean and fat mass), right femur weight and length measurements and Zn concentrations in serum and femur indicated that diets higher in Ca had a more pronounced negative effect on Zn status of rats fed a PA-supplemented diet. Addition of PA to the diet had a greater negative effect on Zn status when Ca concentration in the diet was higher.

Conclusion: These results show that, in rats, higher concentrations of dietary Ca and PA interact to potentiate a decrease in bioavailable Zn and may suggest lower Zn bioavailability in infant cereals with higher PA and Ca concentrations.
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http://dx.doi.org/10.1016/j.jtemb.2020.126643DOI Listing
December 2020

Dietary calcium affects body composition and lipid metabolism in rats.

PLoS One 2019 10;14(1):e0210760. Epub 2019 Jan 10.

Nutrition Research Division, Bureau of Nutritional Sciences, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.

Calcium (Ca) intakes may affect cardiovascular disease risk by altering body composition (body weight and fat) and serum lipid profile, but results have been inconsistent and the underlying mechanisms are not well understood. The effects of dietary Ca on body composition and lipid metabolism were examined in rats. Male Sprague-Dawley rats were fed high-fat, high-energy diets containing (g/kg) low (0.75Ca, 0.86 ± 0.05; 2Ca, 2.26 ± 0.02), normal (5Ca, 5.55 ± 0.08) or high (10Ca, 11.03 ± 0.17; 20Ca, 21.79 ± 0.15) Ca for 10 weeks. Rats fed the lowest Ca diet (0.75Ca) had lower (p < 0.05) body weight and fat mass compared to other groups. Rats fed the high Ca diets had lower serum total and LDL cholesterol compared to rats fed normal or low Ca. Liver total cholesterol was lower in rats fed high compared to low Ca. In general, liver mRNA expression of genes involved in cholesterol uptake from the circulation (Ldlr), cholesterol synthesis (Hmgcr and Hmgcs1), fatty acid oxidation (Cpt2) and cholesterol esterification (Acat2) were higher in rats fed higher Ca. Apparent digestibility of total trans, saturated, monounsaturated and polyunsaturated fatty acids was lower in rats fed the high compared to the low Ca diets, with the largest effects seen on trans and saturated fatty acids. Fecal excretion of cholesterol and total bile acids was highest in rats fed the highest Ca diet (20Ca). The results suggest little effect of dietary Ca on body composition unless Ca intakes are very low. Decreased bile acid reabsorption and reduced absorption of neutral sterols and saturated and trans fatty acids may contribute to the better serum lipid profile in rats fed higher Ca.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210760PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328234PMC
November 2019

Dietary supplementation with L-lysine affects body weight and blood hematological and biochemical parameters in rats.

Mol Biol Rep 2019 Feb 28;46(1):433-442. Epub 2018 Nov 28.

Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada.

L-Lysine (Lys) is a popular additive in foods, but the physiological effects of excess Lys supplementation are poorly understood and upper limits of safe intake have not been established. The objectives of this study were to examine the effects of dietary supplementation with increasing amounts of Lys on body weight (BW), food intake, and various blood hematological and biochemical parameters in rats. Male Sprague-Dawley rats at 10 weeks of age were assigned to ten diet groups (eight rats/group) and fed diets containing either 7% or 20% casein and supplemented with either 0% (Control), 1.5%, 3%, 6% Lys, or 6% Lys + 3% arginine for 1 week. Rats fed 7% casein with ≥ 1.5% Lys supplementation had lower serum albumin and leptin and higher LDL cholesterol (LDLC), ratios of total cholesterol (TC):HDL cholesterol (HDLC) and LDLC:HDLC than those fed 7% casein Control diet (P < 0.05). Rats fed 7% casein diet supplemented with 3% Lys diet had lower BW gain, food intake, serum alkaline phosphatase activity, and increased mean corpuscular hemoglobin concentration, blood urea nitrogen and serum pancreatic polypeptide compared to rats fed the Control diet (P < 0.05). Addition of 6% Lys in 7% casein caused significant BW loss (P < 0.001) and altered additional parameters. Addition of 6% Lys in a 20% casein diet reduced BW gain and food intake and altered numerous parameters. Arg supplementation normalized many of the endpoints changed by Lys. Collectively, these results show that Lys supplementation affects BW, food intake and a number of hematological and biochemical parameters. These effects of Lys supplementation were confined primarily in diets with lower levels of dietary protein. In the context of a low protein diet (7% casein), levels of Lys supplementation ≥ 1.5% may exert adverse health effects in rats.
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http://dx.doi.org/10.1007/s11033-018-4492-1DOI Listing
February 2019

Serum Magnesium Concentrations in the Canadian Population and Associations with Diabetes, Glycemic Regulation, and Insulin Resistance.

Nutrients 2017 Mar 17;9(3). Epub 2017 Mar 17.

Bureau of Food Surveillance and Science Integration, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON K1A 0K9, Canada.

Total serum magnesium (Mg) concentration (SMC) is commonly used to assess Mg status. This study reports current SMCs of Canadians and their associations with demographic factors, diabetes, and measures of glycemic control and insulin resistance using results from the Canadian Health Measures Survey cycle 3 (2012-2013). Associations were examined in adults aged 20-79 years using linear mixed models. Mean SMCs and percentile distributions for 11 sex-age groups between 3 and 79 years ( = 5561) are reported. SMCs were normally distributed and differences ( < 0.05) among sex and age groups were small. Between 9.5% and 16.6% of adult sex-age groups had a SMC below the lower cut-off of a population-based reference interval (0.75-0.955 mmol·L) established in the United States population as part of the NHANES I conducted in 1971-1974. Having diabetes was associated with 0.04 to 0.07 mmol·L lower SMC compared to not having diabetes in the various models. Body mass index, glycated hemoglobin, serum glucose and insulin concentrations, and homeostatic model assessment of insulin resistance were negatively associated with SMC. This is the first study to report SMCs in a nationally representative sample of the Canadian population. A substantial proportion of Canadians are hypomagnesaemic in relation to a population-based reference interval, and SMC was negatively associated with diabetes and indices of glycemic control and insulin resistance.
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http://dx.doi.org/10.3390/nu9030296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372959PMC
March 2017

Moderately Low Magnesium Intake Impairs Growth of Lean Body Mass in Obese-Prone and Obese-Resistant Rats Fed a High-Energy Diet.

Nutrients 2016 Apr 28;8(5). Epub 2016 Apr 28.

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, ON K1A 0K9, Canada.

The physical and biochemical changes resulting from moderately low magnesium (Mg) intake are not fully understood. Obesity and associated co-morbidities affect Mg metabolism and may exacerbate Mg deficiency and physiological effects. Male rats selectively bred for diet-induced obesity (OP, obese-prone) or resistance (OR, obese-resistant) were fed a high-fat, high-energy diet containing moderately low (LMg, 0.116 ± 0.001 g/kg) or normal (NMg, 0.516 ± 0.007 g/kg) Mg for 13 weeks. The growth, body composition, mineral homeostasis, bone development, and glucose metabolism of the rats were examined. OP and OR rats showed differences (p < 0.05) in many physical and biochemical measures regardless of diet. OP and OR rats fed the LMg diet had decreased body weight, lean body mass, decreased femoral size (width, weight, and volume), and serum Mg and potassium concentrations compared to rats fed the NMg diet. The LMg diet increased serum calcium (Ca) concentration in both rat strains with a concomitant decrease in serum parathyroid hormone concentration only in the OR strain. In the femur, Mg concentration was reduced, whereas concentrations of Ca and sodium were increased in both strains fed the LMg diet. Plasma glucose and insulin concentrations in an oral glucose tolerance test were similar in rats fed the LMg or NMg diets. These results show that a moderately low Mg diet impairs the growth of lean body mass and alters femoral geometry and mineral metabolism in OP and OR rats fed a high-energy diet.
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http://dx.doi.org/10.3390/nu8050253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882666PMC
April 2016

l-Lysine supplementation does not affect the bioavailability of copper or iron in rats.

J Trace Elem Med Biol 2016 Dec 24;38:194-200. Epub 2016 Feb 24.

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, K1A 0K9, Canada; Department of Chemistry, Carleton University, Canada. Electronic address:

l-lysine (Lys) is an essential amino acid that is added to foods and dietary supplements. Lys may interact with mineral nutrients and affect their metabolism. This study examined the effect of dietary Lys supplementation on the bioavailability of copper (Cu) and iron (Fe). Weanling male Sprague-Dawley rats were fed one of five diets (20% casein) for 4 weeks containing normal Cu and Fe (control) or low Cu or Fe without (LCu, LFe) or with (LCu+Lys, LFe+Lys) addition of 1.5% Lys. Final body weights, body weight gains and food consumption of the rats did not differ (P≥0.05) among diet groups. Rats fed the low Cu or Fe diets showed changes in nutritional biomarkers compared to control rats, demonstrating reduced Cu and Fe status, respectively. Hematological parameters, serum ceruloplasmin activity and Cu and Fe concentrations in serum, liver, kidney and intestinal mucosa were unaffected (P≥0.05) by Lys supplementation. These results indicate that in the context of an adequate protein diet, Lys supplementation at a relatively high level does not affect Cu or Fe bioavailability in rats.
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http://dx.doi.org/10.1016/j.jtemb.2016.02.005DOI Listing
December 2016

Lower serum magnesium concentration is associated with diabetes, insulin resistance, and obesity in South Asian and white Canadian women but not men.

Food Nutr Res 2015 5;59:25974. Epub 2015 May 5.

Nutrition Research Division, Health Products and Food Branch, Health Canada, Ottawa, Canada.

Background: A large proportion of adults in North America are not meeting recommended intakes for magnesium (Mg). Women and people of South Asian race may be at higher risk for Mg deficiency because of lower Mg intakes relative to requirements and increased susceptibility to diabetes, respectively.

Objective: This study compared serum Mg concentrations in South Asian (n=276) and white (n=315) Canadian women and men aged 20-79 years living in Canada's Capital Region and examined the relationship with diabetes, glucose control, insulin resistance, and body mass index.

Results: Serum Mg concentration was lower in women of both races and South Asians of both genders. Racial differences in serum Mg were not significant after controlling for use of diabetes medication. A substantial proportion of South Asian (18%) and white (9%) women had serum Mg <0.75 mmol/L indicating hypomagnesemia. Use of diabetes medication and indicators of poorer glucose control, insulin resistance, and obesity were associated with lower serum Mg in women, but not in men.

Conclusions: These results suggest that the higher incidence of diabetes in South Asians increases their risk for Mg deficiency and that health conditions that increase Mg requirements have a greater effect on Mg status in women than men.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422846PMC
http://dx.doi.org/10.3402/fnr.v59.25974DOI Listing
May 2015

Bioavailability of magnesium from inorganic and organic compounds is similar in rats fed a high phytic acid diet.

Magnes Res 2014 Oct-Dec;27(4):175-85

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada, K1A 0K9, Food Science and Nutrition Program, Carleton University.

A large section of the North American population is not meeting recommended intakes for magnesium (Mg). Supplementation and consumption of Mg-fortified foods are ways to increase intake. Currently, information on Mg bioavailability from different compounds and their efficacy in improving Mg status is scant. This study compared the relative ability of inorganic and organic Mg compounds to preserve the Mg status of rats when fed at amounts insufficient to retain optimal Mg status. Male Sprague-Dawley rats (n=12/diet group) were fed one of eight test diets supplemented with phytic acid (5 g/kg diet) and low levels of Mg (155 mg elemental Mg/kg diet) from Mg oxide, Mg sulphate, Mg chloride, Mg citrate, Mg gluconate, Mg orotate, Mg malate or ethylenediaminetetraacetic acid disodium Mg salt for five weeks. Rats were also fed three control diets that did not contain added phytic acid but were supplemented with 500 (NMgO, normal), 155 (LMgO, low) or 80 (DMgO, deficient) mg of Mg per kg diet as Mg oxide. Mg concentrations in femur, serum and urine showed a graded decrease in rats fed the control diets with lower Mg. Mg concentrations did not differ (P≥0.05) between rats fed the different test diets. Addition of phytic acid to the diet did not affect the Mg status of the rats. The results indicate that any differences in the Mg bioavailability of the compounds were small and physiologically irrelevant.
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http://dx.doi.org/10.1684/mrh.2014.0374DOI Listing
October 2015

Small increases in dietary calcium above normal requirements exacerbate magnesium deficiency in rats fed a low magnesium diet.

Magnes Res 2014 Jan-Mar;27(1):35-47

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada, K1A 0K9, Food Science and Nutrition Program, Carleton University.

In North America, the calcium (Ca):magnesium (Mg) intake ratio has increased over the last several decades raising concerns about possible adverse effects of Ca intakes on Mg status. The primary objective of this study was to investigate whether small decreases or increases in dietary Ca from normal requirements worsen Mg status in rats fed a low Mg diet. Weanling male Sprague-Dawley rats were fed 1 of 8 diets for 6 weeks. The 7 test diets were supplemented with low Mg (0.18 g/kg diet) and either 1 (1Ca), 3 (3Ca), 5 (5Ca), 7.5 (7.5Ca), 10 (10Ca), 15 (15Ca) or 20 (20Ca) g Ca/kg diet. The control diet was supplemented with normal Mg (0.5 g/kg) and Ca (5 g/kg). Rats fed higher Ca gained less weight and had lower fat mass and energy efficiency. Compared to rats fed normal Ca (5Ca), Mg concentrations in serum and femur were lower in rats fed the higher Ca diets. Haemoglobin and haematocrit were also lower in rats fed the 15Ca and 20Ca diets. Rats fed the 10Ca, 15Ca and 20Ca diets had higher urine Ca compared to rats fed the 5Ca diet. Increase in urine Ca was associated with a rise in urine Mg. The higher Ca diets increased the Ca:Mg molar ratio in serum, femur, heart and kidney. These results suggest that small increases in dietary Ca exacerbate Mg deficiency in rats fed an inadequate Mg diet by reducing intestinal Mg absorption and also by impairing renal Mg reabsorption at higher Ca intakes.
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http://dx.doi.org/10.1684/mrh.2014.0360DOI Listing
February 2015

Diet-induced obese rats have higher iron requirements and are more vulnerable to iron deficiency.

Eur J Nutr 2014 Apr 6;53(3):885-95. Epub 2013 Oct 6.

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, 251 Sir Frederick Banting Driveway, PL 2203E, Ottawa, ON, K1A 0K9, Canada,

Purpose: Since obesity is associated with poorer iron status, the effects of diet-induced obesity on iron status and iron-regulatory pathways were examined.

Methods: Weanling male diet-induced obese sensitive (n = 12/diet group) and resistant (n = 12/diet group) rats were fed one of four high-fat, high-energy diets supplemented with 5 (5Fe, low), 15 (15Fe, marginal), 35 (35Fe, normal) or 70 (70Fe, high) mg iron/kg diet for 12 weeks. At the end of the study, rats in each diet group were categorised as obese (>19 %) or lean (<17 %) based on percentage body fat.

Results: Obese rats gained more weight, had larger total lean mass, consumed more food and showed greater feed efficiency compared with lean rats. Obese rats fed the 5Fe and 15Fe diets had poorer iron status than lean rats fed the same diet. Obese 5Fe rats had lower serum iron and more severe iron-deficiency anaemia. Obese 15Fe rats had lower mean corpuscular haemoglobin and liver iron concentrations. Hepcidin mRNA expression in liver and adipose tissue was similar for obese and lean rats. Iron concentration and content of the iron transporters divalent metal transporter 1 and ferroportin 1 in duodenal mucosa were also similar.

Conclusions: Obese rats that were larger, regardless of adiposity, had higher iron requirements compared with lean rats that appeared independent of hepcidin, inflammation and intestinal iron absorption. Higher iron requirements may have resulted from larger accretion of body mass and blood volume. Greater food consumption did not compensate for the higher iron needs, indicating increased susceptibility to iron deficiency.
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http://dx.doi.org/10.1007/s00394-013-0592-9DOI Listing
April 2014

Mineral concentrations in bottled water products: implications for Canadians' mineral intakes.

Can J Diet Pract Res 2013 ;74(1):46-50

Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON.

Purpose: The popularity of bottled water products (BWPs) is growing in Canada. Concentrations of minerals with important implications for health were compared in different types of BWPs.

Methods: One sample of each brand and type of plain BWP (purified, remineralized, spring, mineral, and artesian), flavoured BWP, and nutrient-enriched BWP sold in major stores in Ottawa, Ontario, was purchased to allow determination of mineral concentrations by flame atomic absorption or emission spectroscopy. A total of 124 BWPs representing 37 brands were analyzed.

Results: In general, spring and mineral water contained higher amounts of magnesium and calcium than did purified, remineralized, artesian, flavoured, or nutrient-enriched water. Most plain BWPs contained little sodium and potassium, whereas 15% to 35% of flavoured and nutrient-enriched products had considerably higher concentrations. Only magnesium and calcium concentrations were highly correlated (r=0.76, p<0.001). Calculation of the percentage of Dietary Reference Intakes that could be supplied by each product revealed that, if they are consumed habitually, many products can contribute substantially to recommended intakes of these minerals.

Conclusions: Mineral concentrations in most types of BWP varied, but distinct differences between types of products were identified. Consumers should be aware of the mineral content of BWPs because some could influence intakes of certain minerals significantly.
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http://dx.doi.org/10.3148/74.1.2013.46DOI Listing
January 2014

Zinc supplementation does not alter sensitive biomarkers of copper status in healthy boys.

J Nutr 2013 Mar 9;143(3):284-9. Epub 2013 Jan 9.

Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, Health Canada, Ottawa, Ontario, Canada.

The tolerable upper intake levels (UL) for zinc for children were based on limited data and there is concern that the UL may be set too low. The first effect of excessive zinc intake is a reduction in copper status. The primary objective of this study was to examine the effect of zinc supplementation on copper status in children. Healthy, 6- to 8-y-old boys from Ontario, Canada were assigned to take a placebo (n = 10) or 5 mg (n = 10), 10 mg (n = 9), or 15 mg (n = 8) of zinc supplement daily for 4 mo in a double-blinded, placebo-controlled, randomized trial. Biochemical measures were evaluated at baseline and after 2 and 4 mo of supplementation. Food records were completed near the baseline and 4-mo visits. Age and anthropometric measurements did not differ (P > 0.05) between treatment groups at baseline. Mean zinc intakes from food alone (10.9-14.8 mg zinc/d) approached or exceeded the UL of 12 mg/d. Compared with the placebo group, the zinc groups had a greater change in the urine zinc:creatinine ratio at 4 mo (P = 0.02). Traditional (plasma copper and ceruloplasmin activity) and more sensitive biomarkers of copper status, including erythrocyte SOD1 activity and the erythrocyte CCS:SOD1 protein ratio, were unchanged in zinc-supplemented boys, demonstrating that copper status was not depressed. Serum lipid measures and hemoglobin concentrations were also unaffected and gastrointestinal symptoms were not reported. These data provide evidence in support of the need for reexamining the current UL for zinc for children.
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http://dx.doi.org/10.3945/jn.112.171306DOI Listing
March 2013

EDTA disodium zinc has superior bioavailability compared to common inorganic or chelated zinc compounds in rats fed a high phytic acid diet.

J Trace Elem Med Biol 2012 Oct 9;26(4):227-33. Epub 2012 May 9.

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, Ottawa, Ontario, Canada.

Different zinc (Zn) compounds have unique properties that may influence the amount of Zn absorbed particularly in the presence of phytic acid (PA), a common food component that binds Zn and decreases its bioavailability. In this study, 30-day-old male rats (n=12/diet group) were fed diets supplemented with PA (0.8%) and low levels (8mg Zn/kg diet) of inorganic (Zn oxide, Zn sulphate) or chelated (Zn gluconate, Zn acetate, Zn citrate, EDTA disodium Zn, Zn orotate) Zn compounds for 5 weeks. Two control groups were fed diets supplemented with low or normal (30mg Zn/kg diet) Zn (as Zn oxide) without added PA. Control rats fed the low Zn oxide diet showed depressed Zn status. Addition of PA to this diet exacerbated the Zn deficiency in rats. Growth (body weight gain and femur length) and Zn concentrations in plasma and tissues were similar in rats fed Zn oxide, Zn sulphate, Zn gluconate, Zn acetate, Zn citrate or Zn orotate. Rats fed EDTA disodium Zn showed enhanced growth compared to rats fed Zn oxide or Zn gluconate and had higher Zn concentrations in plasma and femur compared to rats fed all other Zn compounds. Only the haematological profile of rats fed EDTA disodium Zn did not differ from control rats fed normal Zn. These data indicate that in rats fed a high PA diet, bioavailability of commonly used inorganic or chelated Zn compounds does not differ appreciably, but Zn supplied as an EDTA disodium salt has superior bioavailability.
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http://dx.doi.org/10.1016/j.jtemb.2012.04.008DOI Listing
October 2012

Copper transporter 2 content is lower in liver and heart of copper-deficient rats.

Int J Mol Sci 2010 Nov 19;11(11):4741-9. Epub 2010 Nov 19.

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, K1A 0K9, Canada; E-Mail:

Copper (Cu) transporter 2 (Ctr2) is a transmembrane protein that transports Cu across cell membranes and increases cytosolic Cu levels. Experiments using cell lines have suggested that Ctr2 expression is regulated by Cu status. The importance of changes in Ctr2 expression is underscored by recent studies demonstrating that lower Ctr2 content in cells increases the cellular uptake of platinum-containing cancer drugs and toxicity to the drugs. In this study, we examined whether Ctr2 expression is altered by a nutritional Cu deficiency in vivo. Ctr2 mRNA and protein in liver and heart from rats fed a normal (Cu-N), moderately deficient (Cu-M) or deficient (Cu-D) Cu diet was measured. Rats fed the Cu-deficient diets showed a dose-dependent decrease in liver Ctr2 protein compared to Cu-N rats. Ctr2 protein was 42% and 85% lower in Cu-M and Cu-D rats, respectively. Liver Ctr2 mRNA was 50% lower in Cu-D rats and unaffected in Cu-M rats. In heart, Ctr2 protein was only lower in Cu-D rats (46% lower). These data show that Cu deficiency decreases Ctr2 content in vivo.
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http://dx.doi.org/10.3390/ijms11114741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000112PMC
November 2010

Decreased erythrocyte CCS content is a biomarker of copper overload in rats.

Int J Mol Sci 2010 Jul 2;11(7):2624-35. Epub 2010 Jul 2.

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada; E-Mails: (L.S.); (L.J.P.).

Copper (Cu) is an essential trace metal that is toxic in excess. It is therefore important to be able to accurately assess Cu deficiency or overload. Cu chaperone for Cu/Zn superoxide dismutase (CCS) protein expression is elevated in tissues of Cu-deficient animals. Increased CCS content in erythrocytes is particularly sensitive to decreased Cu status. Given the lack of a non-invasive, sensitive and specific biomarker for the assessment of Cu excess, we investigated whether CCS expression in erythrocytes reflects Cu overload. Rats were fed diets containing normal or high levels of Cu for 13 weeks. Diets contained 6.3 +/- 0.6 (Cu-N), 985 +/- 14 (Cu-1000) or 1944 +/- 19 (Cu-2000) mg Cu/kg diet. Rats showed a variable response to the high Cu diets. Some rats showed severe Cu toxicity, while other rats showed no visible signs of toxicity and grew normally. Also, some rats had high levels of Cu in liver, whereas others had liver Cu concentrations within the normal range. Erythrocyte CCS protein expression was 30% lower in Cu-2000 rats compared to Cu-N rats (P < 0.05). Notably, only rats that accumulated high levels of Cu in liver had lower erythrocyte CCS (47% reduction, P < 0.05) compared to rats fed normal levels of Cu. Together, these data indicate that decreased erythrocyte CCS content is associated with Cu overload in rats and should be evaluated further as a potential biomarker for assessing Cu excess in humans.
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http://dx.doi.org/10.3390/ijms11072624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920556PMC
July 2010

Ctr1 transports silver into mammalian cells.

J Trace Elem Med Biol 2010 Jul 12;24(3):178-84. Epub 2010 Feb 12.

Nutrition Research Division, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.

Silver is a non-essential, toxic metal. The use of silver as an antimicrobial agent in many applications and its presence as a contaminant in foods and air can lead to accumulation in tissues. Despite its widespread use, the systems involved in the uptake of silver into mammalian cells are presently unknown. Previous studies have shown that copper uptake at the plasma membrane by copper transporter 1 (Ctr1) is inhibited by an excess of silver, suggesting that Ctr1 may function in importing silver into cells. In this study we examined directly the role of Ctr1 in the accumulation of silver in mammalian cells using over-expression experiments and mouse embryonic fibroblast cells lacking Ctr1. COS-7 cells transfected to express a human Ctr1-green fluorescent protein (hCtr1-GFP) fusion protein hyper-accumulated silver when incubated in medium supplemented with low micromolar concentrations (2.5-10 micromol/L) of AgNO(3). An hCtr1-GFPM150L,M154L variant deficient for copper transport failed to stimulate accumulation of silver. Mouse embryonic fibroblast cells lacking Ctr1 showed approximately a 50% reduction in silver content when incubated in silver-supplemented medium compared to a wild-type isogenic cell line. Collectively, these data demonstrate that Ctr1 transports both copper and silver and suggest that Ctr1 is an important transport protein in the accumulation of silver in mammalian cells.
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http://dx.doi.org/10.1016/j.jtemb.2010.01.009DOI Listing
July 2010

Considerations in the development of biomarkers of copper status.

J AOAC Int 2009 Sep-Oct;92(5):1541-50

Health Canada, Health Products and Food Branch, Bureau of Nutritional Sciences, Food Directorate, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada, K1A 0K9.

Copper (Cu) is an essential nutrient, but a harmful metal in excess. As part of the North American Dietary Reference Intakes, the Recommended Dietary Allowance for Cu was set using a combination of biomarkers of Cu deficiency, including plasma Cu and ceruloplasmin concentrations, erythrocyte Cu/Zn superoxide dismutase activity, and platelet Cu concentration. Liver damage was the sole indicator used in setting the Tolerable Upper Intake Level. Some studies suggest that these conventional biomarkers may not be sensitive enough to detect marginal reductions or excesses of Cu that could pose a health risk. The insensitivity of conventional biomarkers casts uncertainty as to the prevalence of Cu deficiency or overload in the population and in the accuracy of current nutritional reference values for Cu. Numerous biochemical changes have been associated with alterations in Cu status, and many potential biomarkers of Cu nutriture have been proposed; yet, conventional biomarkers are still the most frequently used, underscoring the need for research efforts to substantiate the use of novel biomarkers. In this report, biomarkers of Cu status are reviewed and practical considerations in the development of novel biomarkers are discussed as diagnostic tools for assessing Cu status in humans.
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December 2009

Regulatory frameworks for copper considering chronic exposures of the population.

Am J Clin Nutr 2008 Sep;88(3):863S-6S

Bureau of Nutritional Sciences, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.

Copper is an essential nutrient that is toxic in excess. Copper intakes from a balanced diet appear to meet the needs of most healthy individuals, because overt deficiency and toxicity are rare. Some uncertainty, however, persists because of limitations in currently available biomarkers used to assess copper status and the paucity of data available to establish tolerable upper levels of intake. Current policies and regulations pertaining to food fortification, nutritional supplements, and drinking water appear to be effective in providing for adequate copper intakes in many populations, although high levels of exposure, through overzealous fortification, supplementation, or drinking water exposure, may be possible under some circumstances. Surveillance and monitoring programs to evaluate copper exposures of human populations should continue and should be refined as new biomarkers become available.
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http://dx.doi.org/10.1093/ajcn/88.3.863SDOI Listing
September 2008

Increased incorporation of dietary plant sterols and cholesterol correlates with decreased expression of hepatic and intestinal Abcg5 and Abcg8 in diabetic BB rats.

J Nutr Biochem 2009 Mar 10;20(3):177-86. Epub 2008 Jun 10.

Banting Research Center, Ottawa, Ontario, Canada.

The aim of this study was to determine the impact of dietary plant sterols and stanols on sterol incorporation and sterol-regulatory gene expression in insulin-treated diabetic rats and nondiabetic control rats. Diabetic BioBreeding (BB) and control BB rats were fed a control diet or a diet supplemented with plant sterols or plant stanols (5 g/kg diet) for 4 weeks. Expression of sterol-regulatory genes in the liver and intestine was assessed by real-time quantitative polymerase chain reaction. Diabetic rats demonstrated increased tissue accumulation of cholesterol and plant sterols and stanols compared to control rats. This increase in cholesterol and plant sterols and stanols was associated with a marked decrease in hepatic and intestinal Abcg5 (ATP-binding cassette transporter G5) and Abcg8 (ATP-binding cassette transporter G8) expressions in diabetic rats, as well as decreased mRNA levels of several other genes involved in sterol regulation. Plant sterol or plant stanol supplementation induced the accumulation of plant sterols and stanols in tissues in both rat strains, but induced a greater accumulation of plant sterols and stanols in diabetic rats than in control rats. Surprisingly, only dietary plant sterols decreased cholesterol levels in diabetic rats, whereas dietary plant stanols caused an increase in cholesterol levels in both diabetic and control rats. Therefore, lower expression levels of Abcg5/Abcg8 in diabetic rats may account for the increased accumulation of plant sterols and cholesterol in these rats.
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http://dx.doi.org/10.1016/j.jnutbio.2008.01.011DOI Listing
March 2009

Ctr2 is partially localized to the plasma membrane and stimulates copper uptake in COS-7 cells.

Biochem J 2008 Feb;409(3):731-40

Nutrition Research Division, Health Products and Food Branch, Health Canada, Sir Frederick G. Banting Research Centre, PL 2203C, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada, K1A 0L2.

Ctr1 (copper transporter 1) mediates high-affinity copper uptake. Ctr2 (copper transporter 2) shares sequence similarity with Ctr1, yet its function in mammalian cells is poorly understood. In African green monkey kidney COS-7 cells and rat tissues, Ctr2 migrated as a predominant band of approximately 70 kDa and was most abundantly expressed in placenta and heart. A transiently expressed hCtr2-GFP (human Ctr2-green fluorescent protein) fusion protein and the endogenous Ctr2 in COS-7 cells were mainly localized to the outer membrane of cytoplasmic vesicles, but were also detected at the plasma membrane. Biotinylation of Ctr2 with the membrane-impermeant reagent sulfo-NHS-SS-biotin [sulfosuccinimidyl-2-(biotinamido)ethyl-1,3-dithiopropionate] confirmed localization at the cell surface. Cells expressing hCtr2-GFP hyperaccumulated copper when incubated in medium supplemented with 10 microM CuSO(4), whereas cells depleted of endogenous Ctr2 by siRNAs (small interfering RNAs) accumulated lower levels of copper. hCtr2-GFP expression did not affect copper efflux, suggesting that hCtr2-GFP increased cellular copper concentrations by promoting uptake at the cell surface. Kinetic analyses showed that hCtr2-GFP stimulated saturable copper uptake with a K(m) of 11.0+/-2.5 microM and a K(0.5) of 6.9+/-0.7 microM when data were fitted to a rectangular hyperbola or Hill equation respectively. Competition experiments revealed that silver completely inhibited hCtr2-GFP-dependent copper uptake, whereas zinc, iron and manganese had no effect on uptake. Furthermore, increased copper concentrations in hCtr2-GFP-expressing cells were inversely correlated with copper chaperone for Cu/Zn superoxide dismutase protein expression. Collectively, these results suggest that Ctr2 promotes copper uptake at the plasma membrane and plays a role in regulating copper levels in COS-7 cells.
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http://dx.doi.org/10.1042/BJ20071025DOI Listing
February 2008

Sparing effects of selenium and ascorbic acid on vitamin C and E in guinea pig tissues.

Nutr J 2007 Mar 26;6. Epub 2007 Mar 26.

Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Sir Frederick G, Banting Research Centre, Ottawa, ON, Canada.

Background: Selenium (Se), vitamin C and vitamin E function as antioxidants within the body. In this study, we investigated the effects of reduced dietary Se and L-ascorbic acid (AA) on vitamin C and alpha-tocopherol (AT) status in guinea pig tissues.

Methods: Male Hartley guinea pigs were orally dosed with a marginal amount of AA and fed a diet deficient (Se-D/MC), marginal (Se-M/MC) or normal (Se-N/MC) in Se. An additional diet group (Se-N/NC) was fed normal Se and dosed with a normal amount of AA. Guinea pigs were killed after 5 or 12 weeks on the experimental diets at 24 and 48 hours post AA dosing.

Results: Liver Se-dependent glutathione peroxidase activity was decreased (P < 0.05) in guinea pigs fed Se or AA restricted diets. Plasma total glutathione concentrations were unaffected (P > 0.05) by reduction in dietary Se or AA. All tissues examined showed a decrease (P < 0.05) in AA content in Se-N/MC compared to Se-N/NC guinea pigs. Kidney, testis, muscle and spleen showed a decreasing trend (P < 0.05) in AA content with decreasing Se in the diet. Dehydroascorbic acid concentrations were decreased (P < 0.05) in several tissues with reduction in dietary Se (heart and spleen) or AA (liver, heart, kidney, muscle and spleen). At week 12, combined dietary restriction of Se and AA decreased AT concentrations in most tissues. In addition, restriction of Se (liver, heart and spleen) and AA (liver, kidney and spleen) separately also reduced AT in tissues.

Conclusion: Together, these data demonstrate sparing effects of Se and AA on vitamin C and AT in guinea pig tissues.
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http://dx.doi.org/10.1186/1475-2891-6-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847450PMC
March 2007

Copper chaperone for Cu/Zn superoxide dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc.

Nutr J 2005 Nov 24;4:35. Epub 2005 Nov 24.

Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, 2203C Banting Research Centre, Ottawa, ON, K1A 0L2, Canada.

Background: Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status.

Methods: Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status.

Results: Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4).

Conclusion: Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn.
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http://dx.doi.org/10.1186/1475-2891-4-35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315358PMC
November 2005

Maintaining copper homeostasis: regulation of copper-trafficking proteins in response to copper deficiency or overload.

J Nutr Biochem 2004 Jun;15(6):316-22

Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, 2203C Banting Research Centre, Ottawa, ON, Canada K1A 0L2.

Copper is an essential micronutrient that plays a vital role as a catalytic co-factor for a variety of metalloenzymes. The redox chemistry of copper also makes it a potentially toxic metal if not properly used. Therefore, elaborate mechanisms have evolved for controlling its cellular uptake, elimination, and distribution. In the last decade, our understanding of the systems involved in maintaining copper homeostasis has improved considerably with the characterization of copper transporters that mediate cellular copper uptake or efflux and with the identification of copper chaperones, a family of proteins required for delivering copper to specific targets in the cell. Despite the distinct roles of these proteins in copper trafficking, all seem able to respond to changes in copper status. Here, we describe recent advances in our knowledge of how copper-trafficking proteins respond to copper deficiency or overload in mammalian cells in order to maintain copper balance.
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http://dx.doi.org/10.1016/j.jnutbio.2004.02.004DOI Listing
June 2004

Copper modulates the degradation of copper chaperone for Cu,Zn superoxide dismutase by the 26 S proteosome.

J Biol Chem 2003 Sep 27;278(37):35071-8. Epub 2003 Jun 27.

Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, 2203C Banting Research Centre, Ottawa, Ontario K1A 0L2, Canada.

Copper chaperones are copper-binding proteins that directly insert copper into specific targets, preventing the accumulation of free copper ions that can be toxic to the cell. Despite considerable advances in the understanding of copper transfer from copper chaperones to their target, to date, there is no information regarding how the activity of these proteins is regulated in higher eukaryotes. The insertion of copper into the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) depends on the copper chaperone for SOD1 (CCS). We have recently reported that CCS protein is increased in tissues of rats fed copper-deficient diets suggesting that copper may regulate CCS expression. Here we show that whereas copper deficiency increased CCS protein in rats, mRNA level was unaffected. Rodent and human cell lines cultured in the presence of the specific copper chelator 2,3,2-tetraamine displayed a dose-dependent increase in CCS protein that could be reversed with the addition of copper but not iron or zinc to the cells. Switching cells from copper-deficient to copper-rich medium promoted the rapid degradation of CCS, which could be blocked by the proteosome inhibitors MG132 and lactacystin but not a cysteine protease inhibitor or inhibitors of the lysosomal degradation pathway. In addition, CCS degradation was slower in copper-deficient cells than in cells cultured in copper-rich medium. Together, these data show that copper regulates CCS expression by modulating its degradation by the 26 S proteosome and suggest a novel role for CCS in prioritizing the utilization of copper when it is scarce.
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http://dx.doi.org/10.1074/jbc.M302242200DOI Listing
September 2003

Evidence implicating Ku antigen as a structural factor in RNA polymerase II-mediated transcription.

Gene 2003 Jan;302(1-2):53-64

Graduate Program in Biochemistry, University of Ottawa, The Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ont. K1Y 4E9, Canada.

Ku antigen is an abundant nuclear protein with multiple functions that depend mainly on Ku's prolific and highly verstatile interactions with DNA. We have shown previously that the direct binding of Ku in vitro to negative regulatory element 1 (NRE1), a transcriptional regulatory element in the long terminal repeat of mouse mammary tumour virus, correlates with the regulation of viral transcription by Ku. In this study, we have sought to explore the interaction of Ku with NRE1 in vivo in yeast one-hybrid experiments. Unexpectedly, we observed that human Ku70 carrying a transcriptional activation domain from the yeast Gal4 protein induced transcription of yeast reporter genes pleiotrophically, independent of NRE1, promoter, reporter gene and chromosomal location. Ku80 with the same activation domain had no effect on transcription when expressed alone, but reconstituted activation when co-expressed with native human Ku70. The requirements for transcriptional activation by Ku-Gal4 activation domain proteins correlated with previous descriptions of the requirements for DNA sequence-independent DNA binding by Ku, but were distinct from determinants for DNA-end binding by a truncated Ku heterodimer determined recently by crystallography. These results suggest a preferential targeting of Ku to transcriptionally active chromatin that indicate a possible function for Ku within the RNA polymerase II holoenzyme.
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http://dx.doi.org/10.1016/s0378111902010892DOI Listing
January 2003

Copper deficiency induces the upregulation of the copper chaperone for Cu/Zn superoxide dismutase in weanling male rats.

J Nutr 2003 Jan;133(1):28-31

Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.

The most commonly used indices for determining copper deficiency in humans are reduced serum/plasma copper concentration and decreased activity of ceruloplasmin and Cu/Zn superoxide dismutase (SOD1). However, these indicators are influenced by many factors unrelated to copper status and lack the sensitivity required to detect marginal deficiency, limiting their usefulness in many situations. In vivo, the insertion of copper into SOD1 is dependent on the copper chaperone for SOD1 (CCS). In this study, we explored the possibility that the expression level of CCS may reflect copper status and thus serve as a useful marker of copper nutriture. Weanling male Wistar rats were fed either a normal (5.3 mg Cu/kg diet), moderately deficient (0.84 mg Cu/kg diet) or deficient (0.34 mg Cu/kg diet) copper diet for 6 wk. Rats fed moderate and deficient diets showed differences (P < 0.05) in several hematological measurements, indicating varying degrees of copper deficiency in these groups. Copper-deficient rats had reduced (P < 0.05) liver and erythrocyte SOD1 activity and body weight. Western blot analysis revealed a dose-dependent increase (P < 0.05) in CCS expression in liver and erythrocytes of copper-deficient rats. We report CCS protein level as a novel marker for assessing copper status.
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http://dx.doi.org/10.1093/jn/133.1.28DOI Listing
January 2003
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