Article

Zinc toxicity alters mitochondrial metabolism and leads to decreased ATP production in hepatocytes

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario P3E 2C6, Canada.
Journal of Applied Toxicology (Impact Factor: 3.17). 03/2008; 28(2):175-82. DOI: 10.1002/jat.1263
Source: PubMed

ABSTRACT Although zinc (Zn) is a known environmental toxicant, its impact on the cellular energy-producing machinery is not well established. This study investigated the influence of this divalent metal on the oxidative ATP producing network in human hepatocellular carcinoma (HepG2) cells. Zn-challenged cells contained more oxidized proteins and lipids compared with control cells. Zn severely impeded mitochondrial functions by inhibiting aconitase, alpha-ketoglutarate dehydrogenase, isocitrate dehydrogenase-NAD+ dependent, succinate dehydrogenase and cytochrome C oxidase Zn-exposed cells had a disparate mitochondrial metabolism compared with the control cells and produced significantly less ATP. However, the expression of isocitrate dehydrogenase-NADP+ dependent was more prominent in cells treated with Zn. Hence, Zn-induced pathologies may be due to the inability of the mitochondria to generate energy effectively.

Download full-text

Full-text

Available from: Joseph Lemire, Jun 21, 2015
0 Followers
 · 
184 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Microalgae are attracting attention due to their potentials in mitigating CO2 emissions and removing environmental pollutants. However, harvesting microalgal biomass from diluted cultures is one of the bottlenecks for developing economically viable processes for this purpose. Microalgal cells can be harvested by cost-effective sedimentation when flocculating strains are used. In this study, the removal of Zn2+ and Cd2+ by the flocculating Chlorella vulgaris JSC-7 was studied. The experimental results indicated that more than 80% Zn2+ and 60% Cd2+ were removed by the microalgal culture within 3 days in the presence up to 20.0 mg/L Zn2+ and 4.0 mg/L Cd2+, respectively, which were much higher than that observed with the culture of the non-flocculating C. vulgaris CNW11. Furthermore, the mechanism underlying this phenomenon was explored by investigating the effect of Zn2+ and Cd2+ on the growth and metabolic activities of the microalgal strains. It was found that the flocculation of the microalga improved its growth, synthesis of photosynthetic pigments and antioxidation activity under the stressful conditions, indicating a better tolerance to the heavy metal ions for a potential in removing them more efficiently from contaminated wastewaters, together with a bioremediation of other nutritional components contributed to the eutrophication of aquatic ecosystems.
    Journal of Hazardous Materials 05/2015; 289:38-45. · 4.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Measuring biological responses in resident biota is a commonly used approach to monitoring polluted habitats. The challenge is to choose sensitive and, ideally, stressor-specific endpoints that reflect the responses of the ecosystem. Metabolomics is a potentially useful approach for identifying sensitive and consistent responses since it provides a holistic view to understanding the effects of exposure to chemicals upon the physiological functioning of organisms. In this study, we exposed the aquatic non-biting midge, Chironomus tepperi, to two concentrations of zinc chloride and measured global changes in polar metabolite levels using an untargeted gas chromatography-mass spectrometry (GC-MS) analysis and a targeted liquid chromatography-mass spectrometry (LC-MS) analysis of amine-containing metabolites. These data were correlated with changes in the expression of a number of target genes. Zinc exposure resulted in a reduction in levels of intermediates in carbohydrate metabolism (i.e., glucose 6-phosphate, fructose 6-phosphate and disaccharides) and an increase in a number of TCA cycle intermediates. Zinc exposure also resulted in decreases in concentrations of the amine containing metabolites, lanthionine, methionine and cystathionine, and an increase in metallothionein gene expression. Methionine and cystathionine are intermediates in the transsulfuration pathway which is involved in the conversion of methionine to cysteine. These responses provide an understanding of the pathways affected by zinc toxicity, and how these effects are different to other heavy metals such as cadmium and copper. The use of complementary metabolomics analytical approaches was particularly useful for understanding the effects of zinc exposure and importantly, identified a suite of candidate biomarkers of zinc exposure useful for the development of biomonitoring programs. Copyright © 2015 Elsevier B.V. All rights reserved.
    Aquatic toxicology (Amsterdam, Netherlands) 03/2015; 162. DOI:10.1016/j.aquatox.2015.03.009 · 3.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Plants have developed several external and internal aluminium (Al) tolerance mechanisms. The external mechanism best characterised is the exudation of organic acids induced by Al. Rye (Secale cereale L.), one of the most Al-tolerant cereal crops, secretes both citrate and malate from its roots in response to Al. However, the role of malate dehydrogenase (MDH) genes in Al-induced stress has not been studied in rye. We have isolated the ScMDH1 and ScMDH2 genes, encoding two different mitochondrial MDH isozymes, in three Al-tolerant rye cultivars (Ailés, Imperial and Petkus) and one sensitive inbred rye line (Riodeva). These genes, which have seven exons and six introns, were located on the 1R (ScMDH1) and 3RL (ScMDH2) chromosomes. Exon 1 of ScMDH1 and exon 7 of ScMDH2 were the most variable among the different ryes. The hypothetical proteins encoded by these genes were classified as putative mitochondrial MDH isoforms. The phylogenetic relationships obtained using both cDNA and protein sequences indicated that the ScMDH1 and ScMDH2 proteins are orthologous to mitochondrial MDH1 and MDH2 proteins of different Poaceae species. The expression studies of the ScMDH1 and ScMDH2 genes indicate that it is more intense in roots than in leaves. Moreover, the amount of their corresponding mRNAs in roots from plants treated and not treated with Al was higher in the tolerant cultivar Petkus than in the sensitive inbred line Riodeva. In addition, ScMDH1 and ScMDH2 mRNA levels decreased in response to Al stress (repressive behaviour) in the roots of both the tolerant Petkus and the sensitive line Riodeva.
    Plant Biology 06/2014; 17(1). DOI:10.1111/plb.12219 · 2.41 Impact Factor