uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Brittlestars contain highly sulfated chondroitin sulfates/dermatan sulfates that promote fibroblast growth factor 2-induced cell signaling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Dorothe Spillmann)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Dorothe Spillmann)
Department of Biological and Environmental Sciences, University of Gothenburg . (Mike Thorndyke)
Department of Biochemistry, Boston University.
Show others and affiliations
2014 (English)In: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 24, no 2, 195-207 p.Article in journal (Refereed) Published
Abstract [en]

Glycosaminoglycans (GAGs) isolated from brittlestars, Echinodermata class Ophiuroidea, were characterized, as part of attempts to understand the evolutionary development of these polysaccharides. A population of chondroitin sulfate/dermatan sulfate (CS/DS) chains with a high overall degree of sulfation and hexuronate epimerization was the major GAG found, whereas heparan sulfate (HS) was below detection level. Enzymatic digestion with different chondroitin lyases revealed exceptionally high proportions of di- and trisulfated CS/DS disaccharides. The latter unit appears much more abundant in one of four individual species of brittlestars, Amphiura filiformis, than reported earlier in other marine invertebrates. The brittlestar CS/DS was further shown to bind to growth factors such as fibroblast growth factor 2 and to promote FGF-stimulated cell signaling in GAG-deficient cell lines in a manner similar to that of heparin. These findings point to a potential biological role for the highly sulfated invertebrate GAGs, similar to those ascribed to HS in vertebrates.

Place, publisher, year, edition, pages
2014. Vol. 24, no 2, 195-207 p.
Keyword [en]
Brittlestar, Chodroitin sulfate, Dermatan sulfate, Fibroblast growth factor-2
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-178989DOI: 10.1093/glycob/cwt100ISI: 000330839300009OAI: oai:DiVA.org:uu-178989DiVA: diva2:543813
Available from: 2012-08-10 Created: 2012-08-06 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Galactosaminoglycans - Role in Brittlestar Limb Regeneration
Open this publication in new window or tab >>Galactosaminoglycans - Role in Brittlestar Limb Regeneration
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Regeneration is, in simple terms, ‘to re-grow’ damaged or lost parts of the body (e.g. cells, tissues and organs) and is a natural phenomenon occurring throughout the life of an organism. The regenerative capacity varies in the animal kingdom. Invertebrates have high regenerative capacity in contrast to higher vertebrates. This raises several fundamental questions related to the regeneration potential, evolutionary selection and its cellular and molecular mechanisms. An in-depth knowledge in regeneration is warranted to answer the fundamental questions that are still a challenge in regenerative medicine.

 Glycosaminoglycans (GAGs) are known to be involved in various physiological processes. Of several GAG types galactosaminoglycans are the focus of this thesis. Galactosaminoglycans such as chondroitin sulfate/dermatan sulfate (CS/DS) are anionic linear polysaccharides covalently linked to core proteins so called proteoglycans (PGs), and form an integral part of both cell surface and extracellular matrix components. Although CS/DS have been associated with different cellular processes from development to homeostasis, not many studies have been carried out to understand their role in regeneration. In this thesis, we aim to study galactosaminoglycans, their structure, and interaction with growth factors of biological importance in the process of regeneration using simple invertebrate model organisms - brittlestars.

We have identified CS/DS as the major GAG present in brittlestars. Molecular characterization of these chains indicated a much higher level of sulfation in Amphiura filiformis than so far found in GAGs from invertebrates or vertebrates. This brittlestar CS/DS promotes FGF2 mediated cell signaling similar to heparin. Further, we studied the functional role of these CS/DS chains and their biosynthetic machinery during arm regeneration in A. filiformis. Regeneration is followed by an increase in GAG sulfation from blastema stage to the fully functional arm. Suppressing sulfation on the other hand by sodium chlorate treatment drastically affected the proliferation process and thereby regeneration. Thus our findings suggest a potential biological role of CS/DS in brittlestar limb regeneration that may have relevance to regenerative medicine in future.

 

 

 

 

 

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 51 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 791
Keyword
Chondroitin sulfate, Dermatan sulfate, Brittlestar, Regeneration
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-179044 (URN)978-91-554-8413-2 (ISBN)
Public defence
2012-09-18, C2:301, BMC, Uppsala University, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2012-08-28 Created: 2012-08-06 Last updated: 2013-01-22Bibliographically approved
2. Brittlestars Galactosaminoglycans and Tools to Study their Structure
Open this publication in new window or tab >>Brittlestars Galactosaminoglycans and Tools to Study their Structure
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In all living organisms, biological activities such as proper functioning and co-ordination of different organs will depend on different cells and molecular interactions. In some organisms the loss of functional organs or damage of organs can be lethal, whereas in others a special process called regeneration can retrieve lost organs. The molecular details of regeneration are still not completely understood in many organisms. Echinoderms are close to vertebrates in the evolutionary tree and are well known for their amazing regeneration capacity. So we chose to investigate the molecular processes of regeneration mechanism with an interest towards our favorite groups of molecules, glycosaminoglycans (GAGs). GAGs are linear polysaccharides, expressed on all cell surfaces and extracellular space and are also known to be involved in many cellular activities. We aimed to characterize the GAGs present in Echinodermata species Amphiura filiformis and investigated their role during arm regeneration.

In Paper I we characterized the structure and function of GAGs from A. filiformis and identified that A. filiformis contains CS/DS type of GAGs, but no HS. The sulfation degree of these CS/DS is close to the one of heparin, i.e. they are highly sulfated. These chains are able to bind FGF-2 growth factor and induce FGF-2 mediated cell signaling. In Paper II we further characterized these GAGs for their localization and for their role in arm regeneration in A. filiformis. Immuno- and histochemical stainings on arm sections revealed that CS/DS GAGs are localized around the podia, surrounding the water vascular system, and around the muscle tissues. Inhibition of sulfated GAG biosynthesis by chlorate treatment affected the regeneration efficiency of the arms, which may be an indication of the importance of CS/DS structures in A. filiformis arm regeneration. We also characterized some bacterial sulfatases in Paper III and a lyase in Paper IV from human and canine gut symbiotic bacteria. Here we sought to find the substrate specificity and optimal conditions for these enzymes’ activities. Our findings suggest that these polysaccharide lyase and sulfatases can be used as potential tools to characterize different GAG structures and their application could further add knowledge on diseases mechanisms related to host pathogen interactions.

 

 

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 63 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1172
Keyword
Chondroitin sulfate, Brittlestars, Gut bacteria, H. bizzozeronii, B.thetaiotaomicron
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Research subject
Biochemistry; Microbiology; Molecular Biology
Identifiers
urn:nbn:se:uu:diva-271559 (URN)978-91-554-9449-0 (ISBN)
Public defence
2016-02-26, A1: 107, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2016-02-02 Created: 2016-01-10 Last updated: 2016-02-12

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Ramachandra, RashmiNamburi, Ramesh BabuLindahl, UlfSpillmann, Dorothe

Search in DiVA

By author/editor
Ramachandra, RashmiNamburi, Ramesh BabuLindahl, UlfSpillmann, Dorothe
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
Glycobiology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 1100 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf