Showing papers by "Christer Hogstrand published in 2014"

Zinc ions modulate protein tyrosine phosphatase 1B activity.

Abstract: Protein tyrosine phosphatases (PTPs) are key enzymes in cellular regulation. The 107 human PTPs are regulated by redox signalling, phosphorylation, dimerisation, and proteolysis. Recent findings of very strong inhibition of some PTPs by zinc ions at concentrations relevant in a cellular environment suggest yet another mechanism of regulation. One of the most extensively investigated PTPs is PTP1B (PTPN1). It regulates the insulin and leptin signalling pathway and is implicated in cancer and obesity/diabetes. The development of novel assay conditions to investigate zinc inhibition of PTP1B provides estimates of about 5.6 nM affinity for inhibitory zinc(II) ions. Analysis of three PTP1B 3D structures (PDB id: 2CM2, 3I80 and 1A5Y) identified putative zinc binding sites and supports the kinetic studies in suggesting an inhibitory zinc only in the closed and cysteinyl–phosphate intermediate forms of the enzyme. These observations gain significance with regard to recent findings of regulatory roles of zinc ions released from the endoplasmic reticulum.

Gill cell culture systems as models for aquatic environmental monitoring

Abstract: A vast number of chemicals require environmental safety assessments for market authorisation. To ensure acceptable water quality, effluents and natural waters are monitored for their potential harmful effects. Tests for market authorisation and environmental monitoring usually involve the use of large numbers of organisms and, for ethical, cost and logistic reasons, there is a drive to develop alternative methods that can predict toxicity to fish without the need to expose any animals. There is therefore a great interest in the potential to use cultured fish cells in chemical toxicity testing. This review summarises the advances made in the area and focuses in particular on a system of cultured fish gill cells grown into an epithelium that permits direct treatment with water samples.

Liver transcriptome analysis of Atlantic cod (Gadus morhua) exposed to PCB 153 indicates effects on cell cycle regulation and lipid metabolism

Abstract: Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) with harmful effects in animals and humans. Although PCB 153 is one of the most abundant among PCBs detected in animal tissues, its mechanism of toxicity is not well understood. Only few studies have been conducted to explore genes and pathways affected by PCB 153 by using high throughput transcriptomics approaches. To obtain better insights into toxicity mechanisms, we treated juvenile Atlantic cod (Gadus morhua) with PCB 153 (0.5, 2 and 8 mg/kg body weight) for 2 weeks and performed gene expression analysis in the liver using oligonucleotide arrays. Whole-genome gene expression analysis detected about 160 differentially regulated genes. Functional enrichment, interactome, network and gene set enrichment analysis of the differentially regulated genes suggested that pathways associated with cell cycle, lipid metabolism, immune response, apoptosis and stress response were among the top significantly enriched. Particularly, genes coding for proteins in DNA replication/cell cycle pathways and enzymes of lipid biosynthesis were up-regulated suggesting increased cell proliferation and lipogenesis, respectively. PCB 153 appears to activate cell proliferation and lipogenic genes in cod liver. Transcriptional up-regulation of marker genes for lipid biosynthesis resembles lipogenic effects previously reported for persistent organic pollutants (POPs) and other environmental chemicals. Our results provide new insights into mechanisms of PCB 153 induced toxicity.

Uptake epithelia behave in a cell-centric and not systems homeostatic manner in response to zinc depletion and supplementation.

Abstract: Much remains to be understood about systemic regulation of zinc uptake in vertebrates, and adequate zinc status is far from always achieved in animals or human. In addition to absorbing zinc from the diet, fish are able to take up zinc directly from the water with the gills. This provides an elegant system to study zinc uptake, how it relates to zinc status, and the expression of genes for proteins involved in zinc acquisition. A 21-day experiment was conducted in which zebrafish were acclimated to deficient, control or excess zinc concentrations in the water and feed. Deficient provision of zinc reduced whole body zinc, potassium, sodium and calcium levels whilst zinc concentrations in the uptake epithelia (gills and gut) remained unchanged. Excess levels of zinc caused accumulation of zinc in the gills, intestine and carcass, but impaired whole body iron, sodium and calcium concentrations. Fish subjected to zinc deficiency had, surprisingly, a reduced zinc influx across the gill epithelium, even when tested at a high concentration of zinc in the water. Zinc influx in the excess group was indistinct from the control. Expression of genes for metallothionein-2 (Mt2) and zinc transporters-1, -2, and -8 (Znt1, Znt2, Znt8) in uptake epithelia showed in general a direct relationship with zinc supply, while mRNA for Zip4 was inversely related to zinc supply. Transcripts for the epithelial calcium channel (Ecac/Trpv6) showed time-dependent increased expression in the gills of the deficiency group, and a transient decrease of expression during zinc excess. Transcriptome profiling by microarrays showed that in both gills and intestine, the most markedly affected biological functions were those related to cell growth, proliferation and cancer, closely followed by processes of gene transcription and protein synthesis in general. Whilst changes in zinc supply had profound effects in the intestine on genes associated with uptake and metabolism of macronutrients, many of the unique categories of genes preferentially regulated in the gill could be mapped onto signalling pathways. This included pathways for PPAR/RXR, LXR/RXR, ATM, chemokine, and BMP signalling. Overall, the responses of epithelial tissue to zinc deficiency and excess are best explained by local epithelial homeostasis with no evidence of systemic control.

Nutritional compositions and antioxidative activities of two blueberry varieties cultivated in South Korea

Abstract: King's College LondonThe nutritional compositions and antioxidative activities of the Kimcheon lowbush and Pyungtaek highbush blueberries cultivated in South Korea were investigated. The approximate compositions, pH, and soluble-solid and mineral contents of P, Ca, Mg, Na, and Zn were determined. Both blueberry cultivars had mainly fructose and glucose as free sugars while disaccharides such as sucrose, maltose, and lactose were not detected in both. Oleic, linoleic, and linolenic fatty acids were the major fatty acids in both types of blueberries. The total of 16 free amino acids, including seven essential and nine non-essential amino acids, were higher in the Pyungtaek highbush blueberry. Among the amino acids, arginine was especially much higher in the Pyungtaek highbush blueberry. The anthocyanin, resveratrol, and polyphenol compounds, which are the important biologically active compounds in blueberries, were found. The anthocyanin contents of the Kimcheon lowbush and Pyungtaek highbush blueberries were 22.0 and 18.1 mg/100 g, respectively; the resveratrol contents by HPLC, 0.12 and 0.11 mg/100 g; and the total polyphenol contents, 141.3 and 138.4 mg/100 g. The electron-donating ability determined based on the DPPH radical scavenging activity was increased in a concentration-dependent manner, and it was higher than that of the Pyungtaek highbush blueberries, which implies that it is highly correlated with the higher amounts of total polyphenol, anthocyanin, and resveratrol in it. In conclusion, the two varieties of Korean blueberries can be suggested as potential sources of high-value-added functional foods.Key words!Korean blueberry, nutritional compositions, resveratrol, anthocyanin, antioxidative activity

Scientific Opinion on the safety and efficacy of iron compounds (E1) as feed additives for all species: ferrous sulphate heptahydrate based on a dossier submitted by Kronos International, Inc.

Abstract: Ferrous sulphate monohydrate is safe when supplied up to a maximum iron content per kilogram complete feedingstuff of 450 mg for bovines and poultry, 500 mg for ovines, 600 mg for pets, and 750 mg for other species/categories, except horses and fish; for piglets up to one week before weaning a maximum of 250 mg Fe/day is considered safe. Because of insufficient data on horses and fish, as a provisional measure, the current value (750 mg Fe/kg) could be maintained. The values for total dietary iron for pigs, ovines, horses, fish and other species/categories (except poultry, bovines and pets) are in line with those currently authorised. Iron from ferrous sulphate monohydrate is unlikely to modify the iron concentration in edible tissues and products of animal origin. Consumer exposure in the EU is not associated with a risk of excess iron intake to the general population. Therefore, the FEEDAP Panel does not foresee any concern for consumer safety resulting from the use of ferrous sulphate monohydrate in animal nutrition, provided that the maximum iron content in complete feedingstuffs is respected. Ferrous sulphate monohydrate is irritant and corrosive to the skin, eyes and respiratory tract. The additive contains up to 109 mg Ni/kg. Nickel is a dermal and respiratory sensitiser, and inhalation may cause lung cancer. Thus, handling the additive poses a risk to the user/worker. Considering the high concentration of iron and sulphur in soil and water, the supplementation of feed with the additive is not expected to pose an environmental risk. Ferrous sulphate monohydrate is an effective iron source for all animal species and categories. The FEEDAP Panel recommends that the currently authorised maximum iron content in complete feed be reduced for bovines and poultry from 750 to 450 mg Fe/kg, and for pets from 1250 to 600 mg Fe/kg. © European Food Safety Authority, 2014

Scientific Opinion on the safety and efficacy of disodium 5′-ribonucleotides, disodium 5′-guanylate, disodium 5′-inosinate for all animal species and categories

Abstract: The flavours included in this assessment are widely present in nature as the building blocks of DNA and RNA. In the absence of any information on the microbial strains or substrates used for the production of the additives, and with little information on the manufacturing process, the FEEDAP Panel is unable to ascertain whether the manufacturing process introduces any safety concerns. Disodium 5′-guanylate and disodium 5′-inosinate and their mixture are considered to be safe for the target animals and the consumer. However, considering the lack of information on the production process, these conclusions apply only to the compounds „per se‟ and their extrapolation to any feed additive containing these compounds is not possible. In the absence of any data related to hazard to the user, it would be prudent to regard disodium 5′-guanylate and disodium 5′-inosinate and their mixture as potentially hazardous to workers by skin or inhalation exposure. The compounds under assessment are naturally present in feed materials; therefore, no risk to the safety for the environment is foreseen. Since these compounds are used in food as flavourings, and their function in feed is essentially the same as that in food, no further demonstration of efficacy is necessary. © European Food Safety Authority, 2014

Scientific Opinion on the safety and efficacy of furanones and tetrahydrofurfuryl derivatives: 5-ethyl-3-hydroxy-4-methylfuran-2(5H)-one and 3-hydroxy-4,5-dimethylfuran-2(5H)-one (chemical group 13) when used as flavourings for all animal species

Abstract: 5-Ethyl-3-hydroxy-4-methylfuran-2(5H)-one and 3-hydroxy-4,5-dimethylfuran-2(5H)-one belong to chemical group 13 (furanones and tetrahydrofurfuryl derivatives) and are authorised for use as flavours in food. These additives are safe at concentrations of 0.05 mg/kg feed for poultry and pigs and 0.08 mg/kg feed for cattle, salmonids and non food-producing animals. The concentration of the additives should be appropriately reduced if used in water for drinking. If used simultaneously in feed and water for drinking, the total intake should not exceed the maximum dose resulting from the use of the flavourings in feed alone. At the levels safe for target animal species these products are safe for the consumers of animal products. The FEEDAP Panel considers it prudent to treat the compounds under assessment as irritant to skin, eyes and the respiratory tract and as skin sensitisers. The proposed concentration of 0.08 mg flavouring compound/kg feed is unlikely to have detrimental effects on the environment except when used in feed for fish in sea cages, in which case the safe concentration would be 0.047 mg/kg. Since both compounds are used in food as flavourings, and their function in feed is essentially the same as that in food, no further demonstration of efficacy is necessary. © European Food Safety Authority, 2014