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| 4. |
- Uebbing, S, et al.
(författare)
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Modulation of microRNA processing by 5-lipoxygenase
- 2021
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 1530-6860. ; 35:2, s. e21193-
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Tidskriftsartikel (refereegranskat)
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| 5. |
- BRUNGS, M, et al.
(författare)
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Sequential induction of 5-lipoxygenase gene expression and activity in Mono Mac 6 cells by transforming growth factor beta and 1,25-dihydroxyvitamin D3
- 1995
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 92:1, s. 107-111
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Tidskriftsartikel (refereegranskat)abstract
- 5-Lipoxygenase (5-LO; EC 1.13.11.34) activity in the human monocytic cell line Mono Mac 6 was upregulated by combined treatment with transforming growth factor beta 1 (TGF-beta) and 1,25-dihydroxyvitamin D3 (VD3). In undifferentiated cells, 5-LO enzyme activity was undetectable. After the addition of TGF-beta plus VD3, the activity of intact cells was 800 ng per 10(6) cells--500 times more than the assay detection limit. Also 5-LO protein and mRNA expression were induced > 128-fold and 64-fold, respectively, as compared to undifferentiated cells. Both TGF-beta and VD3 were required for these prominent responses. Either agent alone gave small amounts of 5-LO protein and mRNA but very low 5-LO activities. After the addition of TGF-beta and VD3, the induction of 5-LO protein was obvious after 1 day, but the increase in activity was delayed and did not appear until the second day. Pretreatment of cells with TGF-beta or VD3 alone for 2 days led to 5-LO protein expression but very low enzyme activity. Addition of the lacking second inducer was required for full induction of 5-LO protein expression and for upregulation of enzyme activity. Partial purification of 5-LO from Mono Mac 6 cells and recombination with soluble cellular proteins from different sources indicated the presence of cytosolic factors that affect the activity of 5-LO.
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| 13. |
- Saul, Meike J., et al.
(författare)
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Mass Spectrometry-Based Proteomics Approach Characterizes the Dual Functionality of miR-328 in Monocytes
- 2019
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Ingår i: Frontiers in Pharmacology. - : FRONTIERS MEDIA SA. - 1663-9812. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRs) are small noncoding RNAs which control the expression of target genes by either translational repression or RNA degradation, known as canonical miR functions. The recent discovery that miR-328 has a noncanonical function and can activate gene expression by antagonizing the activity of heterogeneous ribonuclear protein E2 (hnRNP E2) opens an unexplored and exciting field of gene expression regulation. The global importance of such noncanonical miR function is not yet known. In order to achieve a better understanding of the new miR activity, we performed a compartment specific tandem mass tag (TMT)-based proteomic analysis in differentiated MonoMac6 (MM6) cells, to monitor gene expression variations in response to miR-328 knockdown. We identified a broad spectrum of novel potential miR-328/hnRNP E2 and miR-328 targets involved in regulation of compartment specific cellular processes, such as inflammation or RNA splicing. This study provides first insights of the global significance of noncanonical miR function.
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| 14. |
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| 15. |
- Saul, MJ, et al.
(författare)
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UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 31995-
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Tidskriftsartikel (refereegranskat)abstract
- UPF1 is a key player in nonsense mediated mRNA decay (NMD) but also involved in posttranscriptional gene regulation. In this study we found that UPF1 regulates the expression of genes with functions in inflammation and myeloid cell differentiation via hnRNP E2. The majority of the UPF1-regulated genes identified in monocytic cells contain a binding site for hnRNP E2 within 5′ UTR located introns with hnRNP E2 acting here as splicing regulator. We found that miRNA-328 which is significantly induced during monocytic cell differentiation acts independently from its gene silencing function as RNA decoy for hnRNP E2. One representative gene controlled by the hnRNP E2/miRNA-328 balance is S100A9 which plays an important role in cell differentiation and oxidative stress response of monocytes. Induction of miRNA-328 expression during cell differentiation antagonizes the blockade by hnRNP E2 which results in the upregulation of CD11b expression and ROS production in monocytic cells. Taken together, our data indicate that upregulation of miR-328 is responsible for the induction of hnRNP E2 target genes during myeloid cell differentiation.
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| 16. |
- Schebb, N. H., et al.
(författare)
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Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators-What is the Evidence so far?
- 2022
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Formation of specialized pro-resolving lipid mediators (SPMs) such as lipoxins or resolvins usually involves arachidonic acid 5-lipoxygenase (5-LO, ALOX5) and different types of arachidonic acid 12- and 15-lipoxygenating paralogues (15-LO1, ALOX15; 15-LO2, ALOX15B; 12-LO, ALOX12). Typically, SPMs are thought to be formed via consecutive steps of oxidation of polyenoic fatty acids such as arachidonic acid, eicosapentaenoic acid or docosahexaenoic acid. One hallmark of SPM formation is that reported levels of these lipid mediators are much lower than typical pro-inflammatory mediators including the monohydroxylated fatty acid derivatives (e.g., 5-HETE), leukotrienes or certain cyclooxygenase-derived prostaglandins. Thus, reliable detection and quantification of these metabolites is challenging. This paper is aimed at critically evaluating i) the proposed biosynthetic pathways of SPM formation, ii) the current knowledge on SPM receptors and their signaling cascades and iii) the analytical methods used to quantify these pro-resolving mediators in the context of their instability and their low concentrations. Based on current literature it can be concluded that i) there is at most, a low biosynthetic capacity for SPMs in human leukocytes. ii) The identity and the signaling of the proposed G-protein-coupled SPM receptors have not been supported by studies in knock-out mice and remain to be validated. iii) In humans, SPM levels were neither related to dietary supplementation with their omega-3 polyunsaturated fatty acid precursors nor were they formed during the resolution phase of an evoked inflammatory response. iv) The reported low SPM levels cannot be reliably quantified by means of the most commonly reported methodology. Overall, these questions regarding formation, signaling and occurrence of SPMs challenge their role as endogenous mediators of the resolution of inflammation.
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| 17. |
- Schmidt, G. A., et al.
(författare)
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Climate forcing reconstructions for use in PMIP simulations of the last millennium (v1.0)
- 2011
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 4:1, s. 33-45
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Tidskriftsartikel (refereegranskat)abstract
- Simulations of climate over the Last Millennium (850-1850 CE) have been incorporated into the third phase of the Paleoclimate Modelling Intercomparison Project (PMIP3). The drivers of climate over this period are chiefly orbital, solar, volcanic, changes in land use/land cover and some variation in greenhouse gas levels. While some of these effects can be easily defined, the reconstructions of solar, volcanic and land use-related forcing are more uncertain. We describe here the approach taken in defining the scenarios used in PMIP3, document the forcing reconstructions and discuss likely implications.
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| 18. |
- Schmidt, G. A., et al.
(författare)
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Climate forcing reconstructions for use in PMIP simulations of the last millennium (v1.0)
- 2010
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X. ; 3:3, s. 1549-1586
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Tidskriftsartikel (refereegranskat)abstract
- Simulations of climate over the Last Millennium (850-1850 CE) have been incorporated into the third phase of the Paleoclimate Modelling Intercomparison Project (PMIP3). The drivers of climate over this period are chiefly orbital, solar, volcanic, changes in land use/land cover and some variation in greenhouse gas levels. While some of these effects can be easily defined, the reconstructions of solar, volcanic and land use-related forcing are more uncertain. We describe here the approach taken in defining the scenarios used in PMIP3, document the forcing reconstructions and discuss likely implications.
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| 19. |
- Schmidt, G. A., et al.
(författare)
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Climate forcing reconstructions for use in PMIP simulations of the Last Millennium (v1.1)
- 2012
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 5:1, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- We update the forcings for the PMIP3 experiments for the Last Millennium to include new assessments of historical land use changes and discuss new suggestions for calibrating solar activity proxies to total solar irradiance.
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| 22. |
- Steinhilber, B., et al.
(författare)
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Stiffness, Pain, and Hip Muscle Strength Are Factors Associated With Self-reported Physical Disability in Hip Osteoarthritis
- 2014
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Ingår i: Journal of Geriatric Physical Therapy. - 1539-8412. ; 37:3, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- Background: Physical disability (PD) is common among patients with osteoarthritis (OA) of the hip. Exercise therapy is proposed to be a potential intervention to reduce PD. However, the optimal targets of an exercise program are not known. Purpose: The aim of the present study was to identify factors that explain the level of self-reported PD in patients with hip OA. Knowledge of these factors will help develop specific and effective exercise programs. Methods: Data from 149 patients with hip OA (85 men and 64 women) were analyzed. Self-reported PD was quantified using the physical function subscale of the Western Ontario and McMaster index. A stepwise regression analysis was conducted to identify significant factors associated with self-reported PD. Results: Stiffness, pain, and hip muscle strength were found to be significant factors related to the level of self-reported PD in hip OA. These factors explained 59% (r(2) adjusted = 0.59) of the variance. Body mass index, gender, age, and passive internal hip rotation and flexion range of motion explained only minor parts of the dependent variable self-reported PD. Discussion and Conclusion: Stiffness, pain, and hip muscle strength are associated with self-reported PD in hip OA. It is imperative that exercise treatments for hip OA include strategies to modify these factors. Further research should evaluate their role in preventing hip OA.
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| 23. |
- Werz, O, et al.
(författare)
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Activation of 5-lipoxygenase by cell stress is calcium independent in human polymorphonuclear leukocytes
- 2002
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 99:3, s. 1044-1052
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Tidskriftsartikel (refereegranskat)abstract
- 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory leukotrienes. This study showed that various forms of cell stress, such as chemical stress (sodium arsenite), osmotic stress, or heat shock lead to substantial formation of 5-LO products in freshly isolated human polymorphonuclear leukocytes (PMNLs), when exogenous arachidonic acid (10 μM) was present. In parallel, cell stress led to activation of p38 MAPK (mitogen-activated protein kinase) and mitogen-activated protein kinase-activated protein kinases (MAPKAPKs) kinases, which can phosphorylate 5-LO in vitro. Interestingly, arsenite also caused redistribution of 5-LO from the cytosol to the nuclear membrane. Only minor activation of extracellular signal-regulated kinases and c-jun NH2-terminal kinases was observed, implying that these MAPKs are less important for 5-LO product formation in stress-stimulated PMNLs. Stimulation of 5-LO product formation by Ca++-ionophore A23187 or thapsigargin depended on Ca++; almost no 5-LO product formation was observed in freshly isolated PMNLs when Ca++ was depleted by chelating agents. Also the response toN-formylmethionyl-leucyl-phenylalanine (fMLP) was clearly diminished, but some 5-LO product formation remained. In contrast, stress-induced product formation and translocation of 5-LO, as well as activation of p38 MAPK, occurred also after Ca++ depletion. Moreover, the p38 MAPK inhibitor SB203580 blocked stress-induced 5-LO product formation efficiently, whereas ionophore- or thapsigargin-induced formation of 5-LO products was less sensitive. These data show that cell stress can activate 5-LO in isolated PMNLs by a mechanism that does not involve Ca++ mobilization. This mechanism could function independently of Ca++-mediated 5-LO activation for stimulation of leukotriene biosynthesis under physiologic conditions as well as in inflammatory diseases.
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