liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Westermark , Gunilla
Alternative names
Publications (10 of 70) Show all publications
Nyström, S. N. & Westermark, G. T. (2012). AA-Amyloid is cleared by endogenous immunological mechanisms. Amyloid: Journal of Protein Folding Disorders, 19(3), 138-145.
Open this publication in new window or tab >>AA-Amyloid is cleared by endogenous immunological mechanisms
2012 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no 3, 138-145 p.Article in journal (Refereed) Published
Abstract [en]

Reactive amyloidosis is a complication to longstanding inflammatory diseases.Protein amyloid A (AA), an N-terminal fragment of the acute phase protein serumamyloid A, undergoes conformational changes and is deposited as amyloid in tissue.AA-amyloidosis is reversible and reduction of amyloid mass has been reported as theinflammation ceases. Not much is known about the endogenous factors thatcontribute to amyloid resolution. Herein, we describe the dynamics of amyloiddegradation in experimental murine AA-amyloidosis and show that amyloiddegradation depends on macrophages and antibody formation. AA-amyloidosis wasinduced in mice and resolution of amyloid was monitored over time by histologicaltechniques. Internalized amyloid was present in macrophages that appeared at siteof deposition. At 9 months, when virtually all amyloid was cleared, amyloidosis wasre-induced in one group of animals by a single silver nitrate injection. This causedeposition of excessive amounts of amyloid, and indicate that even thoughundetectable the amyloid reseed in the body and can there act as amyloid enhancingfactor. Antibodies directed against protein AA were detected in animals duringamyloid clearance by ELISA-technique. Passive immunization with an amyloidspecific monoclonal antibody, produced by a B-cell clone recovered from an animalwith advanced AA-amyloidosis, diminish amyloid deposits in murine AA-amyloidosis.Immunoglobulins co-localize with amyloid deposits and can contribute to amyloiddegradation by Fc-receptor mediated phagocytosis.

Keyword
Amyloid A (AA), Amyloid β(Aβ), Amyloid light chain (AL), Alzheimer’s disease (AD), amyloid enhancing factor (AEF), serum amyloid A (SAA), tumour necrosis factor (TNF)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20807 (URN)10.3109/13506129.2012.711391 (DOI)000307635600004 ()
Note

funding agencies|Swedish Research Council|2010-55x-20326-04-3|Swedish Rheumatology Association||

Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2017-12-13Bibliographically approved
Lundmark, K., Vahdat Shariatpanahi, A., Westermark, P. & Westermark, G. T. (2010). Depletion of macrophages influences amyloid deposition in spleen in AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, vol 17, issue , pp 115-115. In: AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS (pp. 115-115). Informa Healthcare, 17.
Open this publication in new window or tab >>Depletion of macrophages influences amyloid deposition in spleen in AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, vol 17, issue , pp 115-115
2010 (English)In: AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, Informa Healthcare , 2010, Vol. 17, 115-115 p.Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Informa Healthcare, 2010
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-60258 (URN)000279801500149 ()
Available from: 2010-10-08 Created: 2010-10-08 Last updated: 2010-10-12
Vahdat Shariatpanahi, A., Lundmark, K. & Westermark, G. T. (2010). Distribution of macrophages in spleen with amyloid in AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, vol 17, issue , pp 99-100. In: AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS (pp. 99-100). Informa Healthcare, 17.
Open this publication in new window or tab >>Distribution of macrophages in spleen with amyloid in AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, vol 17, issue , pp 99-100
2010 (English)In: AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, Informa Healthcare , 2010, Vol. 17, 99-100 p.Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Informa Healthcare, 2010
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-60257 (URN)000279801500117 ()
Available from: 2010-10-08 Created: 2010-10-08 Last updated: 2010-10-12
Schultz, S., Nilsson, P., Thor, S. & Westermark, G. (2010). Fly model of type 2 diabetes: processing of proIAPP makes a difference. Paper presented at XII INTERNATIONAL SYMPOSIUM ON AMYLOIDOSIS, 'From Molecular Mechanisms Toward the Cure of Systemic Amyloidoses', Rome, Italy, April 18–21, 2010. Amyloid: Journal of Protein Folding Disorders, 17(S1), 44-45.
Open this publication in new window or tab >>Fly model of type 2 diabetes: processing of proIAPP makes a difference
2010 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 17, no S1, 44-45 p.Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Patients  with type 2 diabetes  have a marked  reducedbeta cell mass and fail to produce  sufficient amounts of insulin required  for regulation  of glucose home- ostasis. Recent research supports that intracellular aggregation of islet amyloid polypeptide  (IAPP) leads to cell death and therefore makes IAPP aggregation a plausible cause for the beta cell reduction. Little is known about the mechanisms that precede amyloid formation  or which cellular pathways are involved in this process.  To  gain better  understanding we haveestablished  a Drosophila melanogaster model,  where GAL4 drives expression  of UAS-targeted transgenes in a cell or tissue specific pattern. The  fruit fly offers a unique  option  to manipulate any cellular  pathway with  different   genetic   tools.   The   knowledge   that*70%  of all Drosophila  melanogaster genes  have anorthologue in humans  stress  the  potential  for path- ways found in D. melanogaster to be of importance in humans  as well. Transgenic flies expressing  human proIAPP  (the precursor of IAPP)  and IAPP and the non-amyloidogenic mouse IAPP (mIAPP) have been generated.  Expression    of  proIAPP    in   the   brain reduced the lifespan of the fly whereas neither  IAPP nor mIAPP expression influenced survival. Immu- nolabelling  with  an  antibody  raised  against  human IAPP   and   that   cross-reacts    with   murine    IAPP labelled neurons  in all three strains, whereas a concomitant loss of cell nuclei only appeared  during proIAPP and IAPP expression. Furthermore, we detected  an early potentiated activation of the autophagy  pathway  in  proIAPP   flies. Interestingly, even  though  IAPP  expression  was not  related  to  a shorter  lifespan, both IAPP and proIAPP  expression in the  central  nervous  system  led  to  amyloid deposition  in the fat body of the head as shown with Congo  red  and  pFTAA,   a  newly  synthesised luminescent conjugated polymer. Our results de- monstrate that  D. melanogaster has a great  potential as a model  for studies  of proIAPP  and  IAPP expression with subsequent amyloid formation  and connected cellular  response  mechanisms. The  find- ing that proIAPP  aggregation  seems to exert a more toxic  impact  at  a  cellular  level is in  line  with  ourresults from mammalian cell lines.

Place, publisher, year, edition, pages
Informa Healthcare, 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-60255 (URN)10.3109/13506121003737401 (DOI)000279801500016 ()
Conference
XII INTERNATIONAL SYMPOSIUM ON AMYLOIDOSIS, 'From Molecular Mechanisms Toward the Cure of Systemic Amyloidoses', Rome, Italy, April 18–21, 2010
Available from: 2010-10-08 Created: 2010-10-08 Last updated: 2017-12-12Bibliographically approved
Schultz, S., Gu, X., Rusten, T. E., Alenius, M. & Westermark, G. (2010). HIAPP and hproIAPP triggers elective autophagy and inhibit the neuro-­protective effect of autophagy. , 17.
Open this publication in new window or tab >>HIAPP and hproIAPP triggers elective autophagy and inhibit the neuro-­protective effect of autophagy
Show others...
2010 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: Amyloid formation is associated with cell death and islet amyloid is thought to participate in the 50-60% β-cell reduction detected in patients with type 2 diabetes. Islet amyloid polypeptide (IAPP) is the main amyloid protein in the islets of Langerhans. Initial IAPP-amyloid formation is intracellular and part of this amyloid constitutes of proIAPP.

Material & methods: We have established a new model in Drosophila melanogaster where expression of hproIAPP and IAPP results in the formation of amyloid. With this model, we have investigated the effect of protein aggregation on pathways such as ER-stress, unfolded protein response (UPR), apoptosis and autophagy. Important steps in the different pathways were manipulated by RNAi-technique or over- expression of endogenous Drosophila proteins.

Results: Expression of hproIAPP and hIAPP driven to the pdf-neurons led to cell death, but this was without activation of ER-stress, UPR or apoptosis. Aggregated hproIAPP and IAPP, labeled with antibodies against ubiquitin and p62 were accumulated intracellular, a finding that points to an involvement of autophagy. HproIAPP and hIAPP were shown to exert their toxic activity by an intracellular mechanism in contrary to Aβ42 and Aβ42 E22G that exhibit an extracellular toxic activity.

Conclusion: Studies on toxicity suggest that hproIAPP and hIAPP aggregates can occupy the autophagy pathway and prevent maintenance of basal cellular homeostasis. Comparison of proIAPP/IAPP and Aβ42 toxicity shows that amyloid proteins of separate origin can exhibit different toxicity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70093 (URN)
Available from: 2011-08-18 Created: 2011-08-18 Last updated: 2011-08-18Bibliographically approved
Chisalita, S. I., Lindström, T., Eson Jennersjö, P., Paulsson, J., Westermark, G., Olsson, A. & Arnqvist, H. (2009). Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control. Acta Diabetologica, 46(1), 35-42.
Open this publication in new window or tab >>Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control
Show others...
2009 (English)In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 46, no 1, 35-42 p.Article in journal (Refereed) Published
Abstract [en]

Our aim was to study, at the same glycemic control, how treatment with either the insulin secretagogue repaglinide or exogenous insulin aspart affects endogenous insulin secretion, plasma insulin and IAPP (islet amyloid polypeptide) levels, GH-IGF (growth hormone-insulin-like growth factor) axis and plasma lipoprotein concentrations in patients with type 2 diabetes. Five patients, age 65.0 +/- A 4.1 years (mean +/- A SE), body weight 82.5 +/- A 5.0 kg, BMI (body mass index) 27.7 +/- A 1.5 kg/m(2) were treated for 10 weeks with repaglinide or insulin aspart in a randomized, cross-over study. At the end of each treatment a 24-h metabolic profile was performed. Blood glucose, C-peptide, free human insulin, free total (human and analogue) insulin, proinsulin, IAPP, IGF-I, IGFBP-1 (IGF binding protein-1), GHBP (growth hormone binding protein) and plasma lipoprotein concentrations were measured. Similar 24-h blood glucose profiles were obtained with repaglinide and insulin aspart treatment. During the repaglinide treatment, the meal related peaks of C-peptide and free human insulin were about twofold higher than during treatment with insulin aspart. Proinsulin, GHBP were higher and IAPP levels tended to be higher during repaglinide compared to insulin aspart. Postprandial plasma total cholesterol, triglycerides and apolipoprotein B concentrations were higher on repaglinide than on insulin aspart treatment. Our results show that, at the same glycemic control, treatment with exogenous insulin aspart in comparison with the insulin secretagogue repaglinide result in a lower endogenous insulin secretion, and a tendency towards a less atherogenic postprandial lipid profile.

Keyword
Insulin secretagogue, Insulin-like growth factor, Lipoprotein
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-16891 (URN)10.1007/s00592-008-0055-6 (DOI)000263001000005 ()
Note

The original publication is available at www.springerlink.com: Ioana Simona Chisalita, Torbjörn Lindström, Pär Eson Jennersjö, Johan Paulsson, Gunilla Westermark, Anders Olsson and Hans Arnqvist, Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control, 2009, ACTA DIABETOLOGICA, (46), 1, 35-42. http://dx.doi.org/10.1007/s00592-008-0055-6 Copyright: Springer -- Verlag http://www.springerlink.com/

Available from: 2009-02-26 Created: 2009-02-20 Last updated: 2017-12-13Bibliographically approved
Schultz, S. & Westermark , G. (2009). Drosophila melanogaster - a model system for protein aggregation. In: The 12th European Drosophila Neurobiology Conference 6-10 September 2008 Wuerzburg, Germany: in: Journal of Neurogenetics, Volume 23 Supplement 1 2009 (pp. S12-S12). , 23.
Open this publication in new window or tab >>Drosophila melanogaster - a model system for protein aggregation
2009 (English)In: The 12th European Drosophila Neurobiology Conference 6-10 September 2008 Wuerzburg, Germany: in: Journal of Neurogenetics, Volume 23 Supplement 1 2009, 2009, Vol. 23, S12-S12 p.Conference paper, Published paper (Refereed)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17148 (URN)
Available from: 2009-03-07 Created: 2009-03-07 Last updated: 2009-03-09
Westermark, P., Lundmark, K. & Westermark, G. (2009). Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model. PLoS ONE, 4(6), e6041.
Open this publication in new window or tab >>Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model
2009 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 4, no 6, e6041- p.Article in journal (Refereed) Published
Abstract [en]

Background: Mouse AA-amyloidosis is a transmissible disease by a prion-like mechanism where amyloid fibrils act by seeding. Synthetic peptides with no amyloid relationship can assemble into amyloid-like fibrils and these may have seeding capacity for amyloid proteins. Principal Findings: Several synthetic peptides, designed for nanotechnology, have been examined for their ability to produce fibrils with Congo red affinity and concomitant green birefringence, affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown that some amphiphilic fibril-forming peptides not only produced Congo red birefringence and showed affinity for thioflavin S, but they also shortened the lag phase for systemic AA-amyloidosis in mice when they were given intravenously at the time of inflammatory induction with silver nitride. Peptides, not forming amyloid-like fibrils, did not have such properties. Conclusions: These observations should caution researchers and those who work with synthetic peptides and their derivatives to be aware of the potential health concerns. © 2009 Westermark et al.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21313 (URN)10.1371/journal.pone.0006041 (DOI)
Note
Original Publication: P. Westermark, Katarzyna Lundmark and Gunilla Westermark, Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model, 2009, PLoS ONE, (4), 6, e6041. http://dx.doi.org/10.1371/journal.pone.0006041 Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2009-10-03
Westermark, G. & Westermark, P. (2009). Serum amyloid A and protein AA: Molecular mechanisms of a transmissible amyloidosis. FEBS Letters, 583(16), 2685-2690.
Open this publication in new window or tab >>Serum amyloid A and protein AA: Molecular mechanisms of a transmissible amyloidosis
2009 (English)In: FEBS Letters, ISSN 0014-5793, Vol. 583, no 16, 2685-2690 p.Article, review/survey (Refereed) Published
Abstract [en]

Systemic AA-amyloidosis is a complication of chronic inflammatory diseases and the fibril protein AA derives from the acute phase reactant serum AA. AA-amyloidosis can be induced in mice by an inflammatory challenge. The lag phase before amyloid develops can be dramatically shortened by administration of a small amount of amyloid fibrils. Systemic AA-amyloidosis is transmissible in mice and may be so in humans. Since transmission can cross species barriers it is possible that AA-amyloidosis can be induced by amyloid in food, e.g. foie gras. In mice, development of AA-amyloidosis can also be accelerated by other components with amyloid-like properties. A new possible risk factor may appear with synthetically made fibrils from short peptides, constructed for tissue repair.

Keyword
Amyloid; Fibril; Prion; Seeding; Transmission
National Category
Cell and Molecular Biology Neurosciences
Identifiers
urn:nbn:se:liu:diva-21254 (URN)10.1016/j.febslet.2009.04.026 (DOI)000269836900015 ()19393650 (PubMedID)
Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2018-01-13
Lundberg, E., Olofsson, A., Westermark, G. & Sauer-Eriksson , A. E. (2009). Stability and fibril formation properties of human and fish transthyretin, and of the Escherichia coli transthyretin-related protein. FEBS JOURNAL, 276(7), 1999-2011.
Open this publication in new window or tab >>Stability and fibril formation properties of human and fish transthyretin, and of the Escherichia coli transthyretin-related protein
2009 (English)In: FEBS JOURNAL, ISSN 1742-464X , Vol. 276, no 7, 1999-2011 p.Article in journal (Refereed) Published
Abstract [en]

Human transthyretin (hTTR) is one of several proteins known to cause amyloid disease. Conformational changes in its native structure result in aggregation of the protein, leading to insoluble amyloid fibrils. The transthyretin (TTR)-related proteins comprise a protein family of 5-hydroxyisourate hydrolases with structural similarity to TTR. In this study, we tested the amyloidogenic properties, if any, of sea bream TTR (sbTTR) and Escherichia coli transthyretin-related protein (ecTRP), which share 52% and 30% sequence identity, respectively, with hTTR. We obtained filamentous structures from all three proteins under various conditions, but, interestingly, different structures displayed different tinctorial properties. hTTR and sbTTR formed thin, curved fibrils at low pH (pH 2-3) that bound thioflavin-T (thioflavin-T-positive) but did not stain with Congo Red (CR) (CR-negative). Aggregates formed at the slightly higher pH of 4.0-5.5 had different morphology, displaying predominantly amorphous structures. CR-positive material of hTTR was found in this material, in agreement with previous results. ecTRP remained soluble at pH 2-12 at ambient temperatures. By raising of the temperature, fibril formation could be induced at neutral pH in all three proteins. Most of these temperature-induced fibrils were thicker and straighter than the in vitro fibrils seen at low pH. In other words, the temperature-induced fibrils were more similar to fibrils seen in vivo. The melting temperature of ecTRP was 66.7 degrees C. This is approximately 30 degrees C lower than the melting temperatures of sbTTR and hTTR. Information from the crystal structures was used to identify possible explanations for the reduced thermostability of ecTRP.

Keyword
amyloid, fibril formation, HIU hydrolase, transthyretin, transthyretin-related protein
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17511 (URN)10.1111/j.1742-4658.2009.06936.x (DOI)
Available from: 2009-03-27 Created: 2009-03-27 Last updated: 2009-03-27
Organisations

Search in DiVA

Show all publications