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Larsson, Göran
Publications (10 of 31) Show all publications
Kerje, S., Hellman, U., Do, L., Larsson, G., Kämpe, O., Engström-Laurent, A. & Lindqvist, U. (2016). Is low molecular hyaluronan an early indicator of disease in avian systemic sclerosis?. Connective Tissue Research, 57(5), 337-346
Open this publication in new window or tab >>Is low molecular hyaluronan an early indicator of disease in avian systemic sclerosis?
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2016 (English)In: Connective Tissue Research, ISSN 0300-8207, E-ISSN 1607-8438, Vol. 57, no 5, p. 337-346Article in journal (Refereed) Published
Abstract [en]

AIM OF THE STUDY: To further elucidate the pathogenesis of systemic sclerosis (SSc) an experimental avian model was used. University of California at Davies line 200-chicken (UCD-200) spontaneously develops a SSc like disease that has most features of human SSc with vascular effects, inflammation, autoimmunity and fibrosis. The first signs of disease in UCD-200 are swelling and ischemic lesions of the comb, a tissue containing high amounts of the glycosaminoglycan hyaluronan. The aim was to evaluate inflammatory and fibrotic processes of the disease with regard to the molecular weight of hyaluronan.

MATERIAL AND METHODS: Comb biopsies from UCD-200 and healthy White Leghorn (WL) chickens as controls at different ages were studied with histochemical localization of hyaluronan, hyaluronidase 1, CD3, IgY and collagen I and III. Hyaluronan molecular weight distribution was estimated with gas phase electrophoretic analysis.

RESULTS: At 2 days of age hyaluronan was visualized in UCD-200 at the dermal part of the comb with no simultaneous staining of Hyal-1. In adult UCD-200 the comb skin was almost totally devoid of hyaluronan compared to WL of the same age. An increase of low molecular weight (LMW) hyaluronan was detected in comb tissue from UCD-200 at 1 day, 1, 2, 4 weeks in contrast to adult animals.

CONCLUSIONS: An early inflammatory process involving LMW hyaluronan was confirmed as a possible profibrotic process. This indicates that hyaluronan might be an important participant in early inflammatory events of SSc in UCD-200 chicken and that disappearance of hyaluronan in skin predisposes to fibrosis.

Place, publisher, year, edition, pages
Taylor & Francis, 2016
Keywords
Avian model, hyaluronan, inflammation, systemic sclerosis, UCD-200 chicken
National Category
Other Basic Medicine Orthopaedics Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-121000 (URN)10.1080/03008207.2016.1182997 (DOI)000383444600002 ()27135250 (PubMedID)
Available from: 2016-05-24 Created: 2016-05-24 Last updated: 2018-06-07Bibliographically approved
Do, L., Dahl, C. P., Kerje, S., Hansell, P., Mörner, S., Lindqvist, U., . . . Hellman, U. (2015). High Sensitivity Method to Estimate Distribution of Hyaluronan Molecular Sizes in Small Biological Samples Using Gas-Phase Electrophoretic Mobility Molecular Analysis.. International Journal of Cell Biology, Article ID 938013.
Open this publication in new window or tab >>High Sensitivity Method to Estimate Distribution of Hyaluronan Molecular Sizes in Small Biological Samples Using Gas-Phase Electrophoretic Mobility Molecular Analysis.
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2015 (English)In: International Journal of Cell Biology, ISSN 1687-8876, E-ISSN 1687-8884, article id 938013Article in journal (Refereed) Published
Abstract [en]

Hyaluronan is a negatively charged polydisperse polysaccharide where both its size and tissue concentration play an important role in many physiological and pathological processes. The various functions of hyaluronan depend on its molecular size. Up to now, it has been difficult to study the role of hyaluronan in diseases with pathological changes in the extracellular matrix where availability is low or tissue samples are small. Difficulty to obtain large enough biopsies from human diseased tissue or tissue from animal models has also restricted the study of hyaluronan. In this paper, we demonstrate that gas-phase electrophoretic molecular mobility analyzer (GEMMA) can be used to estimate the distribution of hyaluronan molecular sizes in biological samples with a limited amount of hyaluronan. The low detection level of the GEMMA method allows for estimation of hyaluronan molecular sizes from different parts of small organs. Hence, the GEMMA method opens opportunity to attain a profile over the distribution of hyaluronan molecular sizes and estimate changes caused by disease or experimental conditions that has not been possible to obtain before.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-111029 (URN)10.1155/2015/938013 (DOI)26448761 (PubMedID)
Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2018-06-07Bibliographically approved
Gennebäck, N., Hellman, U., Malm, L., Larsson, G., Ronquist, G., Waldenström, A. & Mörner, S. (2013). Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes. Journal of Extracellular Vesicles, 2
Open this publication in new window or tab >>Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes
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2013 (English)In: Journal of Extracellular Vesicles, ISSN 2001-3078, E-ISSN 2001-3078, Vol. 2Article in journal (Refereed) Published
Abstract [en]

Exosomes are nano-sized extracellular vesicles, released from various cells, which can stimulate or repress responses in targets cells. We recently reported that cultured cardiomyocytes are able to release exosomes and that they, in turn, are involved in facilitating events in target cells by alteration of gene expression. We investigated whether external stimuli of the cardiomyocyte might influence the transcriptional content of the released exosomes. Exosomes were isolated from media collected from cultured cardiomyocytes (HL-1) with or without growth factor treatment (TGF-β2 and PDGF-BB), with a series of differential centrifugations, including preparative ultracentrifugation and separation with a sucrose gradient. The exosomes were characterized with dynamic light scattering (DLS), electron microscopy (EM) and Western blot and analyzed with Illumina whole genome microarray gene expression. The exosomes were rounded in shape and had an average size of 50-90 nm in diameter with no difference between treatment groups. Analysis of the mRNA content in repeated experiments conclusively revealed 505 transcripts in the control group, 562 in the TGF-β2-treated group and 300 in the PDGF-BB-treated group. Common transcripts (217) were found in all 3 groups. We show that the mode of stimulation of parental cells affects the characteristics of exosomes released. Hence, there is a difference in mRNA content between exosomes derived from cultured cardiomyocytes stimulated, or not stimulated, with growth factors. We also conclude that all exosomes contain a basic package consisting of ribosomal transcripts and mRNAs coding for proteins with functions within the energy supply system.

Place, publisher, year, edition, pages
Co-action publishing, 2013
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-107997 (URN)10.3402/jev.v2i0.20167 (DOI)24009898 (PubMedID)
Available from: 2015-09-01 Created: 2015-09-01 Last updated: 2018-06-07Bibliographically approved
Mirotti, L., Florsheim, E., Rundqvist, L., Larsson, G., Spinozzi, F., Leite-de-Moraes, M., . . . Alcocer, M. (2013). Lipids are required for the development of Brazil nut allergy: the role of mouse and human iNKT cells. Allergy. European Journal of Allergy and Clinical Immunology, 68(1), 74-83
Open this publication in new window or tab >>Lipids are required for the development of Brazil nut allergy: the role of mouse and human iNKT cells
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2013 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no 1, p. 74-83Article in journal (Refereed) Published
Abstract [en]

Background Lipids are required for mice sensitization to Ber e 1, Brazil nut major allergen. Here, we characterized different lipid fractions extracted from Brazil nuts and the lipid-binding ability of Ber e 1. Further, we determined their in vivo ability to induce Ber-specific anaphylactic antibodies and the role of invariant natural killer T (iNKT) cells in this process.

Methods Wild-type (WT) and iNKT cell-deficient mice were sensitized with Ber e 1 and specific lipid fractions, and anaphylactic antibodies were measured by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA). The lipid-binding characteristic of Ber e 1 (Ber) was established by using fluorescent probes and 15N-labeled NMR. In vitro production of IL-4 was determined in Ber/lipid C-stimulated mouse iNKT cells and human T-cell lines containing NKTs primed with CD1d+C1R transfectants by flow cytometry and ELISA, respectively.

Results Only one specific lipid fraction (lipid C), containing neutral and common phospholipids, induced Ber anaphylactic antibodies in mice. Ber e 1 has a lipid-binding site, and our results indicated an interaction between Ber e 1 and lipid C. iNKT-deficient mice produced lower levels of anaphylactic antibodies than WT mice. In vitro, Ber/lipid C-stimulated murine iNKT cells produced IL-4 but not IFN-gamma. Human T-cell lines derived from nut-allergic patients produced IL-4 to Ber/lipid C in a CD1d- and dose-dependent manner.

Conclusion Lipid fraction C from Brazil nut presents an essential adjuvant activity to Ber e 1 sensitization, and iNKT cells play a critical role in the development of Brazil nut-allergic response.

Place, publisher, year, edition, pages
Hoboken, NJ, USA: Wiley-Blackwell, 2013
Keywords
anaphylactic antibodies, food allergy, humans, lipids, NKT cells
National Category
Respiratory Medicine and Allergy Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-63751 (URN)10.1111/all.12057 (DOI)000311974500009 ()
Available from: 2013-01-10 Created: 2013-01-07 Last updated: 2018-06-08Bibliographically approved
Horvath, I., Sellstedt, M., Weise, C., Nordvall, L.-M., Golla, K. P., Olofsson, A., . . . Wittung-Stafshede, P. (2013). Modulation of α-synuclein fibrillization by ring-fused 2-pyridones: templation and inhibition involve oligomers with different structure. Archives of Biochemistry and Biophysics, 532(2), 84-90
Open this publication in new window or tab >>Modulation of α-synuclein fibrillization by ring-fused 2-pyridones: templation and inhibition involve oligomers with different structure
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2013 (English)In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, E-ISSN 1096-0384, Vol. 532, no 2, p. 84-90Article in journal (Refereed) Published
Abstract [en]

In a recent study we discovered that a ring-fused 2-pyridone compound triggered fibrillization of a key protein in Parkinson's disease, α-synuclein. To reveal how variations in compound structure affect protein aggregation, we now prepared a number of strategic analogs and tested their effects on α-synuclein amyloid fiber formation in vitro. We find that, in contrast to the earlier templating effect, some analogs inhibit α-synuclein fibrillization. For both templating and inhibiting compounds, the key species formed in the reactions are α-synuclein oligomers that contain compound. Despite similar macroscopic appearance, the templating and inhibiting oligomers are distinctly different in secondary structure content. When the inhibitory oligomers are added in seed amounts, they inhibit fresh α-synuclein aggregation reactions. Our study demonstrates that small chemical changes to the same central fragment can result in opposite effects on protein aggregation.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
α-synuclein, amyloid, oligomer, protein aggregation, spectroscopy, 2-pyridone
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-66116 (URN)10.1016/j.abb.2013.01.012 (DOI)000317257700004 ()23399432 (PubMedID)
Available from: 2013-02-14 Created: 2013-02-14 Last updated: 2018-06-08Bibliographically approved
Alcocer, M., Rundqvist, L. & Larsson, G. (2012). Ber e 1 protein: the versatile major allergen from Brazil nut seeds.. Biotechnology letters, 34(4), 597-610
Open this publication in new window or tab >>Ber e 1 protein: the versatile major allergen from Brazil nut seeds.
2012 (English)In: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 34, no 4, p. 597-610Article in journal (Refereed) Published
Abstract [en]

Due mainly to its extremely high content of sulphur amino acids, Ber e 1 protein, the major allergen from Brazil nut, has attracted much scientific and press attention. Ber e 1 was the main target protein in early biotechnology transgenic work, in early processing studies of plant storage proteins, in plant vacuolar targeting studies and as the main protein in early nutritional supplementation experiments. Ber e 1 was also one of the first food allergens to be unintentionally transferred from one plant to another and was involved in the first reported case of systemic allergic reaction caused by a food allergen transferred in semen. In this review, many of the Ber e 1 unique biotechnological and structural functions are discussed with a particular emphasis on its use as model protein for studies of intrinsic allergenicity of food proteins.

Place, publisher, year, edition, pages
Dordrecht: Springer Netherlands, 2012
Keywords
2S Albumin, Allergenicity, Food allergen, Supplementation
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-53195 (URN)10.1007/s10529-011-0831-1 (DOI)22187079 (PubMedID)
Available from: 2012-03-15 Created: 2012-03-15 Last updated: 2018-06-08Bibliographically approved
Malm, L., Hellman, U. & Larsson, G. (2012). Size determination of hyaluronan using a gas-phase electrophoretic mobility molecular analysis. Glycobiology, 22(1), 7-11
Open this publication in new window or tab >>Size determination of hyaluronan using a gas-phase electrophoretic mobility molecular analysis
2012 (English)In: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 22, no 1, p. 7-11Article in journal (Refereed) Published
Abstract [en]

Hyaluronan (HA) is a linear non-sulfated polysaccharide mainly found in the extracellular matrix. The size of HA can vary from a fewq saccharides up to at least 25,000 units, reaching molecular weights of 10x103 kDa. HA has mainly biological functions, and both its size and tissue concentration play an important role in many physiological and phatological processes. It is relatively easy ti determine the HA concentration using enzyme-linked binding protein assays, but the molecular weight of HA has so far been shown to be a more challenging task to measure. Here, we present a method for size determination of HA using gas-phase electrophoretic mobility molecular analysis (GEMMA), which utilizes the electrophoretic mobility of molecules in air to estimate the molecular weight of the analyte. We show that this method gives reliable molecular weight estimations of HA in the range 30-2400 kDa, which covers almost its whole biological range. The average measuring time for one GEMMA spectrum is between 5 and 10 min using only 6 pg of HA. In addition the peak area in a GEMMA spectrum can be used to estimate the HA concentration in the sample. The high sensitivity and small sample volumes make GEMMA an excellent tool for both size determination and estimation of concentration of samples with low HA concentration, as is the case for HA extracted from small tissue samples.

Place, publisher, year, edition, pages
Oxford: Oxford University Press, 2012
Keywords
Hyaluronan, gas-phase electrophotretic mobility molecular analyzer, HA size, molecular weight
National Category
Physical Chemistry
Research subject
Medical Biochemistry
Identifiers
urn:nbn:se:umu:diva-46590 (URN)10.1093/glycob/cwr096 (DOI)000297864400003 ()21752866 (PubMedID)
Available from: 2011-09-09 Created: 2011-09-07 Last updated: 2018-06-08Bibliographically approved
Rundqvist, L., Tengel, T., Zdunek, J., Björn, E., Schleucher, J., Alcocer, M. J. & Larsson, G. (2012). Solution structure, copper binding and backbone dynamics of recombinant Ber e 1: the major allergen from brazil nut. PLoS ONE, 7(10), e46435
Open this publication in new window or tab >>Solution structure, copper binding and backbone dynamics of recombinant Ber e 1: the major allergen from brazil nut
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 10, p. e46435-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The 2S albumin Ber e 1 is the major allergen in Brazil nuts. Previous findings indicated that the protein alone does not cause an allergenic response in mice, but the addition of components from a Brazil nut lipid fraction were required. Structural details of Ber e 1 may contribute to the understanding of the allergenic properties of the protein and its potential interaction partners. METHODOLOGY/PRINCIPAL FINDINGS: The solution structure of recombinant Ber e 1 was solved using NMR spectroscopy and measurements of the protein back bone dynamics at a residue-specific level were extracted using (15)N-spin relaxation. A hydrophobic cavity was identified in the structure of Ber e 1. Using the paramagnetic relaxation enhancement property of Cu(2+) in conjunction with NMR, it was shown that Ber e 1 is able to specifically interact with the divalent copper ion and the binding site was modeled into the structure. The IgE binding region as well as the copper binding site show increased dynamics on both fast ps-ns timescale as well as slower µs-ms timescale. CONCLUSIONS/SIGNIFICANCE: The overall fold of Ber e 1 is similar to other 2S albumins, but the hydrophobic cavity resembles that of a homologous non-specific lipid transfer protein. Ber e 1 is the first 2S albumin shown to interact with Cu(2+) ions. This Cu(2+) binding has minimal effect on the electrostatic potential on the surface of the protein, but the charge distribution within the hydrophobic cavity is significantly altered. As the hydrophobic cavity is likely to be involved in a putative lipid interaction the Cu(2+) can in turn affect the interaction that is essential to provoke an allergenic response.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science, 2012
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-60707 (URN)10.1371/journal.pone.0046435 (DOI)000309580800019 ()23056307 (PubMedID)
Available from: 2012-10-29 Created: 2012-10-23 Last updated: 2018-06-08Bibliographically approved
Alcocer, M. J., Murtagh, G. J., Mirotti, L., Brans, A., Harnett, W., Rundqvist, L. & Larsson, G. (2011). The allergenicity of 2S plant albumins. Clinical and Experimental Allergy, 41(12), 1827-1827
Open this publication in new window or tab >>The allergenicity of 2S plant albumins
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2011 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, no 12, p. 1827-1827Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2011
National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-50686 (URN)000297283800035 ()
Note
Abstract från Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology, Nottingham, England, Juli 11-13, 2011 Available from: 2011-12-20 Created: 2011-12-19 Last updated: 2018-06-08Bibliographically approved
Przygodzka, P., Ramstedt, B., Tengel, T., Larsson, G. & Wilczynska, M. (2010). Bomapin is a redox-sensitive nuclear serpin that affects responsiveness of myeloid progenitor cells to growth environment. BMC Cell Biology, 11, 30
Open this publication in new window or tab >>Bomapin is a redox-sensitive nuclear serpin that affects responsiveness of myeloid progenitor cells to growth environment
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2010 (English)In: BMC Cell Biology, ISSN 1471-2121, E-ISSN 1471-2121, Vol. 11, p. 30-Article in journal (Refereed) Published
Abstract [en]

Background: Haematopoiesis is a process of formation of mature blood cells from hematopoietic progenitors in bone marrow. Haematopoietic progenitors are stimulated by growth factors and cytokines to proliferate and differentiate, and they die via apoptosis when these factors are depleted. An aberrant response to growth environment may lead to haematological disorders. Bomapin (serpinb10) is a hematopoietic- and myeloid leukaemia-specific protease inhibitor with unknown function.

Results: We found that the majority of naturally expressed bomapin was located in the nucleus. Both the natural and recombinant bomapin had a disulfide bond which linked the only two bomapin cysteines: one located in the CD-loop and the other near the C-terminus. Computer modelling showed that the cysteines are distant in the reduced bomapin, but can easily be disulfide-linked without distortion of the overall bomapin structure. Low-level ectopic expression of bomapin in bomapin-deficient K562 cells resulted in about 90% increased cell proliferation under normal growth conditions. On the other hand, antisense-downregulation of natural bomapin in U937 cells resulted in a decreased cell proliferation. Bomapin C395S mutant, representing the reduced form of the serpin, had no effect on cell proliferation, suggesting that the disulfide bond-linked conformation of bomapin is biologically important. The bomapin-dependent effect was specific for myeloid cells, since ectopic expression of the serpin in HT1080 cells did not change cell proliferation. In contrast to the survival-promoting activity of bomapin in cells cultured under optimal growth conditions, bomapin enhanced cell apoptosis following growth factor withdrawal.

Conclusions: We propose that bomapin is a redox-sensitive nuclear serpin that augments proliferation or apoptosis of leukaemia cells, depending on growth factors availability.

Place, publisher, year, edition, pages
BioMed Central, 2010
National Category
Biophysics Medical Biotechnology
Research subject
Medical Biochemistry
Identifiers
urn:nbn:se:umu:diva-41118 (URN)10.1186/1471-2121-11-30 (DOI)000278367600001 ()20433722 (PubMedID)
Available from: 2011-03-18 Created: 2011-03-18 Last updated: 2018-06-08Bibliographically approved
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