Publications

Abstract (Expand)

PCB 153 is one of the most abundant PCB congeners detected in biological samples. It is a persistent compound that is still present in the environment despite the ban on production and use of PCBs in the late 1970s. It has strong tendencies to bioaccumulate and biomagnify in biota, and studies have suggested that it is an endocrine and metabolic disruptor. In order to study mechanisms of toxicity, we exposed Atlantic cod (Gadus morhua) to various doses of PCB 153 (0, 0.5, 2 and 8 mg/kg body weight) for two weeks and examined the effects on expression of liver proteins using label-free quantitative proteomics. Label-free liquid chromatography-mass spectrometry analysis of the liver proteome resulted in the quantification of 1272 proteins, of which 78 proteins were differentially regulated in the PCB 153-treated dose groups compared to the control group. Functional enrichment analysis showed that pathways significantly affected are related to the lipid metabolism, cytoskeletal remodeling, cell cycle and cell adhesion. Importantly, the main effects appear to be on lipid metabolism, with up-regulation of enzymes in the de novo fatty acid synthesis pathway, consistent with previous transcriptomics results. Increased plasma triglyceride levels were also observed in the PCB 153 treated fish, in agreement with the induction of the lipogenic genes and proteins. The results suggest that PCB 153 perturbs lipid metabolism in the Atlantic cod liver. Elevated levels of lipogenic enzymes and plasma triglycerides further suggest increased synthesis of fatty acids and triglycerides.

Author: Fekadu Yadetie, Eystein Oveland, Anne Døskeland, Frode Berven Anders Goksøyr, Odd André Karlsen

Date Published: 1st Apr 2017

Journal: Aquatic Toxicology

Abstract (Expand)

BACKGROUND: Methylmecury (MeHg) is a widely distributed environmental pollutant with considerable risk to both human health and wildlife. To gain better insight into the underlying mechanisms of MeHg-mediated toxicity, we have used label-free quantitative mass spectrometry to analyze the liver proteome of Atlantic cod (Gadus morhua) exposed in vivo to MeHg (0, 0.5, 2 mg/kg body weight) for 2 weeks. RESULTS: Out of a toltal of 1143 proteins quantified, 125 proteins were differentially regulated between MeHg-treated samples and controls. Using various bioinformatics tools, we performed gene ontology, pathway and network enrichment analysis, which indicated that proteins and pathways mainly related to energy metabolism, antioxidant defense, cytoskeleton remodeling, and protein synthesis were regulated in the hepatic proteome after MeHg exposure. Comparison with previous gene expression data strengthened these results, and further supported that MeHg predominantly affects many energy metabolism pathways, presumably through its strong induction of oxidative stress. Some enzymes known to have functionally important oxidation-sensitive cysteine residues in other animals are among the differentially regulated proteins, suggesting their modulations by MeHg-induced oxidative stress. Integrated analysis of the proteomics dataset combined with previous gene expression dataset showed a more pronounced effect of MeHg on amino acid, glucose and fatty acid metabolic pathways, and suggested possible interactions of the cellular energy metabolism and antioxidant defense pathways. CONCLUSIONS: MeHg disrupts mainly redox homeostasis and energy generating metabolic pathways in cod liver. The energy pathways appear to be modulated through MeHg-induced oxidative stress, possibly mediated by oxidation sensitive enzymes.

Authors: Fekadu Yadetie, S. Bjorneklett, H. K. Garberg, E. Oveland, F. Berven, A. Goksoyr, O. A. Karlsen

Date Published: 9th Aug 2016

Journal: BMC Genomics

Abstract (Expand)

We propose a hierarchical modelling approach to construct models for disease states at the whole-body level. Such models can simulate effects of drug-induced inhibition of reaction steps on the whole-body physiology. We illustrate the approach for glucose metabolism in malaria patients, by merging two detailed kinetic models for glucose metabolism in the parasite Plasmodium falciparum and the human red blood cell with a coarse-grained model for whole-body glucose metabolism. In addition we use a genome-scale metabolic model for the parasite to predict amino acid production profiles by the malaria parasite that can be used as a complex biomarker.

Authors: Jacky Snoep, Kathleen Green, J. Eicher, D. C. Palm, G. Penkler, F. du Toit, N. Walters, R. Burger, H. V. Westerhoff, Dawie Van Niekerk

Date Published: 27th Nov 2015

Journal: Biochemical Society Transactions

Abstract

Not specified

Authors: J. G. Caporaso, J. Kuczynski, J. Stombaugh, K. Bittinger, F. D. Bushman, E. K. Costello, N. Fierer, A. G. Pena, J. K. Goodrich, J. I. Gordon, G. A. Huttley, S. T. Kelley, D. Knights, J. E. Koenig, R. E. Ley, C. A. Lozupone, D. McDonald, B. D. Muegge, M. Pirrung, J. Reeder, J. R. Sevinsky, P. J. Turnbaugh, W. A. Walters, J. Widmann, T. Yatsunenko, J. Zaneveld, R. Knight

Date Published: 11th Apr 2010

Journal: Nat Methods

Abstract (Expand)

A quantitative proteomic analysis of the membrane of the archaeon Sulfolobus solfataricus P2 using iTRAQ was successfully demonstrated in this technical note. The estimated number of membrane proteins of this organism is 883 (predicted based on Gravy score), corresponding to 30% of the total number of proteins. Using a modified iTRAQ protocol for membrane protein analysis, of the 284 proteins detected, 246 proteins were identified as membrane proteins, while using an original iTRAQ protocol, 147 proteins were detected with only 133 proteins being identified as membrane proteins. Furthermore, 97.2% of proteins identified in the modified protocol contained more than 2 distinct peptides compared to the original workflow. The successful application of this modified protocol offers a potential technique for quantitatively analyzing membrane-associated proteomes of organisms in the archaeal kingdom. The combination of 3 different iTRAQ experiments resulted in the detection of 395 proteins (>or=2 distinct peptides) of which 373 had predicted membrane properties. Approximately 20% of the quantified proteins were observed to exhibit >or=1.5-fold differential expression at temperatures well below the optimum for growth.

Authors: None

Date Published: 4th Dec 2009

Journal: J. Proteome Res.

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