| 1. |
- Olsson, Jenny, et al.
(författare)
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Expression of neutrophil SOD2 is reduced after lipopolysaccharide stimulation : A potential cause of neutrophil dysfunction in chronic kidney disease
- 2011
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 26:7, s. 2195-2201
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Tidskriftsartikel (refereegranskat)abstract
- Background. Neutrophils from patients with chronic kidney disease (CKD) are dysfunctional and thus a contributing factor to the risk of infections. The mechanisms for leucocyte dysfunction in CKD are not fully understood. It is known that lipopolysaccharide (LPS) activates transcription of several genes encoding proinflammatory cytokines. We therefore aimed to study the effect of LPS on neutrophil expression of genes related to the inflammatory response to address the hypothesis that LPS-induced gene transcriptions are altered in CKD patients.Methods. We analysed gene expression of LPS-stimulated neutrophils from 30 patients with CKD and 15 healthy controls. Superoxide dismutase-2 (SOD2), IL1A, IL-1R1, IL-1R2 and IL8RA gene expression from both neutrophils and differentiated HL60 cells were measured by quantitative polymerase chain reaction. Differentiated HL60 cells were stimulated with phorbol-12-myristate-7- acetate (PMA) after inhibition of SOD2 by small interfering RNA followed by respiratory burst assessment using flow cytometry.Results. LPS stimulation induced a significant mobilization of CD11b on neutrophils from CKD and healthy controls. Upregulation of SOD2, IL1A, IL-1R1 and IL-1R2 gene expression in neutrophils from healthy controls after LPS stimulation was contrasted by no change in gene transcription (IL-1R1 and IL-1R2) or even a downregulation in patients with CKD (SOD2 and IL1A). Inhibition of SOD2 reduced the PMA-induced respiratory burst and IL1A, IL-1R1, IL-1R2 and IL8RA gene expression in neutrophil-differentiated HL60 cells.Conclusions. Because of the critical role of SOD2 in the generation of hydrogen peroxide during phagocytosis, downregulation of SOD2 gene expression after LPS stimulation in neutrophils from patients with CKD indicates a potential mechanism for neutrophil dysfunction and cytokine dysregulation in these patients.
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| 3. |
- Andersson, Stefanie, 1989, et al.
(författare)
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Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity
- 2021
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 134:11
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Tidskriftsartikel (refereegranskat)abstract
- The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis. This article has an associated First Person interview with the first authors of the paper.
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| 4. |
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| 5. |
- Bengtsson, Therese, et al.
(författare)
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Proteomics and transcriptomics of the BABA-induced resistance response in potato using a novel functional annotation approach
- 2014
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Induced resistance (IR) can be part of a sustainable plant protection strategy against important plant diseases. beta-aminobutyric acid (BABA) can induce resistance in a wide range of plants against several types of pathogens, including potato infected with Phytophthora infestans. However, the molecular mechanisms behind this are unclear and seem to be dependent on the system studied. To elucidate the defence responses activated by BABA in potato, a genome-wide transcript microarray analysis in combination with label-free quantitative proteomics analysis of the apoplast secretome were performed two days after treatment of the leaf canopy with BABA at two concentrations, 1 and 10 mM. Results: Over 5000 transcripts were differentially expressed and over 90 secretome proteins changed in abundance indicating a massive activation of defence mechanisms with 10 mM BABA, the concentration effective against late blight disease. To aid analysis, we present a more comprehensive functional annotation of the microarray probes and gene models by retrieving information from orthologous gene families across 26 sequenced plant genomes. The new annotation provided GO terms to 8616 previously un-annotated probes. Conclusions: BABA at 10 mM affected several processes related to plant hormones and amino acid metabolism. A major accumulation of PR proteins was also evident, and in the mevalonate pathway, genes involved in sterol biosynthesis were down-regulated, whereas several enzymes involved in the sesquiterpene phytoalexin biosynthesis were up-regulated. Interestingly, abscisic acid (ABA) responsive genes were not as clearly regulated by BABA in potato as previously reported in Arabidopsis. Together these findings provide candidates and markers for improved resistance in potato, one of the most important crops in the world.
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| 7. |
- Berg, Lotta, et al.
(författare)
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Yttrande från SLUs vetenskapliga råd för djurskydd om hållande av hund och katt
- 2018
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Detta yttrande är skrivet på uppdrag av Jordbruksverket i samband med verkets översyn av föreskrifterna för hund och katt. För att Jordbruksverkets föreskrifter ska vara väl förankrade i den senaste forskningen önskar verket inhämta underlag från det vetenskapliga rådet för djurskydd vid Sveriges lantbruksuniversitet, specifikt gällande områdena rörelsebehov, social kontakt och avvänjning.
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| 8. |
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| 9. |
- Jacobson, Therese, et al.
(författare)
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Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast.
- 2012
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Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 125:21, s. 5073-83
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Tidskriftsartikel (refereegranskat)abstract
- Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.
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| 10. |
- Jacobson, Therese, 1976-
(författare)
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Assessing environmental and contaminant stressors in a benthic amphipod
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organisms in the aquatic environment encounter numerous stressors throughout their lifespan. Some of them are biotic such as food availability, predators and parasites. Others are abiotic and include shifting salinity and temperature change among others. Stressors with anthropogenic origin (for example pollution) add to these challenges and can interfere with the organisms´ ability to adapt, survive and successfully reproduce. This thesis focuses on the benthic amphipod Monoporeia affinis and how it responds to environmental (food availability and increased temperature) and contaminant (fenarimol, PFOS and TBT) stressors. M. affinis is a key species in the soft bottoms of the Baltic Sea and inland lakes in Scandinavia. It is considered particularly sensitive to contaminant exposure, especially during the reproduction. The animals were exposed to both single and combined stressors in soft-bottom microcosms during sexual maturation and mating. Adverse effects on survival and reproduction as well as parasite infection, hormonal status and protein damage were analyzed and evaluated for potential population effects and any synergisms between stressors. Results from these studies give support to M. affinis being a sensitive crustacean in terms of contaminant stress. Female sexual maturation is reliant on sufficient food availability and sexual maturation in both sexes is vulnerable to increased water temperatures affecting reproduction fitness. Increased water temperature also acts synergistically with contaminant stress in decreasing the amount of viable eggs and embryos. Ecologically realistic concentrations of perfluorooctane sulfonate (PFOS) and tributyltin (TBT) severely increase the number of parasite infected animals. These results indicate that the M. affinis populations in the field could be adversely affected by pollutant exposure. Effects that could be enhanced by the predicted increase in water temperature due to global warming.
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