Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effects of acute dietary zinc depletion on the gene expression profile of whole blood in human male adults

ABSTRACT: Even though the importance of adequate zinc intake has been known for around half a century, a reliable diagnostic tool to assess the dietary zinc status of individual humans or populations is in absence. The specific aim of this study was to examine differential expression of specific gene transcripts that occur when the dietary intake of zinc is acutely reduced below the dietary requirement for a period of ten days. Gene expression profiles of whole blood collected before and after dietary zinc restriction were determined by microarray analyses. The data provide potential signature genes of suboptimal zinc consumption and relevant bioinformatic interpretation indicate immune response and cell cycle regulation as biological processes associated with the zinc-responsive genes. To identify candidate markers holding the potential to indicate zinc status, a 24-day observational study comprised of acclimation (7 d; 10.4 mg Zn/d), zinc depletion (10 d; 0.3 mg Zn/d), and zinc repletion (7 d; 29.5 mg Zn/d) phases was conducted with healthy male subjects (n = 9). On day 0, 6 and 10 of zinc depletion, whole blood was collectedunder morning fasting state. RNA profiles were stabilized by using PAXgene reagents during the collection process and globin RNA reduction was conducted to improve the detection of transcripts at low abundance. Genes responding to dietary zinc restriction were determined by array results from individual samples collected before and after 10 d of zinc depletion. Pooled RNA samples from each day of blood collection, i.e., baseline, 6 d and 10 d of depletion, respectively, were used to determine the temporal expression pattern of the zinc-responsive genes during dietary zinc depletion.

ORGANISM(S): Homo sapiens

SUBMITTER: Robert Cousins

PROVIDER: E-GEOD-33174 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Zinc (Zn) is a major elemental component of respirable ambient particulate matter (PM) detected often at alarming levels in urban air. Exposure to PM has been widely associated with increased cardiovascular morbidity and mortality, however, it is not known what components or sources of PM are causative. We recently demonstrated that long-term episodic inhalation of combustion PM, having similar amount of Zn found in urban PM, caused myocardial lesions in rats. We further demonstrated that a single pulmonary exposure to Zn at high concentration is associated with disturbances in cardiac mitochondrial function, ion channel regulation, calcium homeostasis, and cell signaling. Therefore, in this study we investigated the role of PM-associated Zn in cardiac injury using multiple exposure scenarios. Male Wistar-Kyoto (WKY) rats of 12-14 wks age were intratracheally exposed (once per wk x 8 or16 wks) to either (1) saline (control); (2) PM having no soluble Zn; (3) combustion PM suspension containing 14.5 ug/mg water-soluble Zn at high and (4) low dose levels, (5) the aqueous fraction of this suspension devoid of solid insoluble particulate fraction (14.5 ug/mg soluble Zn), or (6) Zn sulfate. Zn concentrations were identical in groups 3, 5 and 6. Pulmonary toxicity was apparent in all exposure groups when compared to saline as determined by recovery of cells in bronchoalveolar lavage fluid. Long-term exposure to PM with or without soluble Zn, or Zn sulfate caused distinct myocardial lesions characterized by subepicardial and randomly distributed myocardial inflammation, degeneration, and fibrosis. The lesion severity was higher in those groups receiving Zn PM. Because cardiac mitochondria are likely the primary target of inhaled metal or other absorbed PM components, we analyzed mitochondrial DNA damage using QPCR and found that all exposure groups except those exposed to PM without Zn caused variable degree of damage. Aconitase activity, sensitive to inhibition by oxidative stress was inhibited slightly but significantly in rats receiving zinc sulfate. Although modest, microarray (Affymetrix) analysis revealed expression changes in the heart reflective of effects on cell signaling, inflammation/oxidative stress, mitochondrial fatty acid metabolisms and cell cycle regulation in rats exposed to zinc sulfate. However, these changes were minimal following exposure to PM devoid of soluble metals. We demonstrate that episodic subchronic pulmonary exposure to zinc sulfate causes cardiac injury and mitochondrial DNA damage. Thus, water-soluble PM-associated zinc may be one of the PM components responsible for cardiovascular morbidity. Experiment Overall Design: Group 1 received Saline to serve as a control. Group 2 received Mount St. Helenâs ash, which does not contain any water-soluble zinc or other metals such that we can delineate any cardiac effect secondary to pulmonary deposition of these particles as these fine mode particles themselves are not likely to translocate to the heart. Group 3 received whole saline suspension of the same fugitive oil combustion particle sample used in the previous study, which contained insoluble components plus water-soluble zinc (Kodavanti et al., 2003; 14.5 ug/mg zinc) and also a small amount of water-soluble nickel (3.0 Âµg/mg). Elemental composition of this PM is comparable to Ottawa urban PM (Kodavanti et al., 2003). Group 4 also received same particle sample but at half the dose than group 3. Group 5 received saline-soluble or leachable fraction of PM-HD devoid of any solid material but contained soluble components including zinc and nickel. And, group 6 received zinc sulfate at concentration that was present in groups 3 or 5. This design allowed us to test if cardiac injury in rats was due to leached of zinc or solid particles. There were 4 replicates per treatment group.

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Effects of acute dietary zinc depletion on the gene expression profile of whole blood in human male adults

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