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Functional properties of galectin-3. Beyond the sugar binding.

Lepur, Adriana LU (2012) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2012:68.
Abstract (Swedish)
Popular Abstract in Uncoded languages

Kronična upala je u podlozi mnogih bolesti modernog čovjeka kao što su djiabetes, astma, ateroskleroza itd. Upalu predvode različiti tkivni makrofagi. Proteini iz porodice galektina, proizvedeni u makrofagima, dodatno pridonose razvoju bolesti, stoga je od velikog interesa odgonetnuti različite funkcije galektina. Ovaj rad nastoji identificirati specifične uloge galektina-3 u različito aktiviranim makrofagima te razumjeti mehanizam i posljedice vezanja galektina-3 za ligand.

U prvom radu proučavali smo endocitozu galektina-3 u različito aktiviranim makrofagima. Vidjeli smo da upalni, M1, i alternativno aktivirani, M2, makrofagi proizvode i izlučuju galektin-3 te također mogu... (More)
Popular Abstract in Uncoded languages

Kronična upala je u podlozi mnogih bolesti modernog čovjeka kao što su djiabetes, astma, ateroskleroza itd. Upalu predvode različiti tkivni makrofagi. Proteini iz porodice galektina, proizvedeni u makrofagima, dodatno pridonose razvoju bolesti, stoga je od velikog interesa odgonetnuti različite funkcije galektina. Ovaj rad nastoji identificirati specifične uloge galektina-3 u različito aktiviranim makrofagima te razumjeti mehanizam i posljedice vezanja galektina-3 za ligand.

U prvom radu proučavali smo endocitozu galektina-3 u različito aktiviranim makrofagima. Vidjeli smo da upalni, M1, i alternativno aktivirani, M2, makrofagi proizvode i izlučuju galektin-3 te također mogu endocitozom unositi velike količine galektina-3 dodanog iz vana. Domena koja prepoznaje ugljikohidrat galektina-3 (CRD) nije bila neophodna za endocitozu.

Drugi rad proučava mehanizam kojim galektin-1 usmjerava endocitozu hemoglobinsko-haptoglobinskog kompleksa u M2 makrofagima. Rezultati ukazuju da se galektin-1 dijelom veže na kompleks te ga usmjerva unutar stanice, zaobilazeći put razgradnje, možda u korist recikliranja.

Treći rad bavi se samozdruživanjem galektina-3 koje se ostvaruje kroz međusobnu interkaciju CRD galektina-3. Takav tip samozdruživanja (tip-C) može inicirati samo određeni tip složenog ugljikohidratnog liganda. U vezanje je uključeno više molekula galektina-3 nego što je rasploživog liganda, stoga proces podržava brzu mobilizaciju galktina-3.

U zadnjem radu testirali smo nekolicinu biljnih prerađevina u potrazi za galektinskim inhibitorima. Pokazali smo da određeni biljni produkti vrlo slabo djeluju na nekoliko testiranih galektina. Djelotvnorni galektinski inhibitori su i potencijalni protuupalni lijelovi te bi njihov pronalazak i razvoj mogao biti od velike koristi. (Less)
Abstract
Contemporary diseases like diabetes, asthma, atherosclerosis etc. are marked by chronic inflammation, often supported by the activity of different macrophages. Proteins from galectin family were found to contribute to disease pathophysiology. Therefore, there is an intensive interest in understanding different galectin functions. The aim of this thesis was to pin-point specific galectin-3 roles in differently activated macrophages. Additional aim was to understand the mechanism and consequences of galectin-3 ligand binding.

In the first paper galectin-3 endocytosis was studied in a system of differently activated macrophages. We found that inflammatory, M1, and alternatively activated, M2, macrophages have a large capacity to... (More)
Contemporary diseases like diabetes, asthma, atherosclerosis etc. are marked by chronic inflammation, often supported by the activity of different macrophages. Proteins from galectin family were found to contribute to disease pathophysiology. Therefore, there is an intensive interest in understanding different galectin functions. The aim of this thesis was to pin-point specific galectin-3 roles in differently activated macrophages. Additional aim was to understand the mechanism and consequences of galectin-3 ligand binding.

In the first paper galectin-3 endocytosis was studied in a system of differently activated macrophages. We found that inflammatory, M1, and alternatively activated, M2, macrophages have a large capacity to internalize externally added galectin-3, besides expressing and secreting galectin-3. Additionally, we found that galectin-3 does not require the functional carbohydrate recognition domain (CRD) for its endocytosis.

In the second paper we used M2 macrophages to study how galectin-1 directs the endocytosis of hemoglobin-haptoglobin complex. Our results indicated that galectin-1 bound fraction of the complex takes a recycling intracellular route instead of the pathway for degradation.

The third paper shows how certain complex carbohydrate ligands can induce galectin-3 self-association that involves CRD to CRD binding. This “type-C” self-association engages more galectin-3 molecules than there are available glycan ligands and can explain certain biological events that require fast galectin-3 mobilization.

In the fourth paper we tested the inhibitory potential of a few plant products for several galectins. We found that their activity was very weak, hence the search for more potent anti-galectin, perhaps also anti-inflammatory remedies continues. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Schedin-Weiss, Sophia, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Novum, Huddinge, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
galectin-3, galectin-1, M1 macrophage, M2 macrophage, self-association, fluorescence anisotropy, citrus pectin, galactomannane
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2012:68
pages
71 pages
publisher
Department of Laboratory Medicine, Lund University
defense location
Belfragesalen BMC D15 Lund
defense date
2012-10-05 13:00
ISSN
1652-8220
ISBN
978-91-87189-31-9
language
English
LU publication?
yes
id
6c52b959-b2d8-4810-8c7b-ece15b50d6f9 (old id 3048521)
date added to LUP
2012-09-06 13:20:02
date last changed
2016-09-19 08:44:46
@phdthesis{6c52b959-b2d8-4810-8c7b-ece15b50d6f9,
  abstract     = {Contemporary diseases like diabetes, asthma, atherosclerosis etc. are marked by chronic inflammation, often supported by the activity of different macrophages. Proteins from galectin family were found to contribute to disease pathophysiology. Therefore, there is an intensive interest in understanding different galectin functions. The aim of this thesis was to pin-point specific galectin-3 roles in differently activated macrophages. Additional aim was to understand the mechanism and consequences of galectin-3 ligand binding.<br/><br>
In the first paper galectin-3 endocytosis was studied in a system of differently activated macrophages. We found that inflammatory, M1, and alternatively activated, M2, macrophages have a large capacity to internalize externally added galectin-3, besides expressing and secreting galectin-3. Additionally, we found that galectin-3 does not require the functional carbohydrate recognition domain (CRD) for its endocytosis. <br/><br>
In the second paper we used M2 macrophages to study how galectin-1 directs the endocytosis of hemoglobin-haptoglobin complex. Our results indicated that galectin-1 bound fraction of the complex takes a recycling intracellular route instead of the pathway for degradation. <br/><br>
The third paper shows how certain complex carbohydrate ligands can induce galectin-3 self-association that involves CRD to CRD binding. This “type-C” self-association engages more galectin-3 molecules than there are available glycan ligands and can explain certain biological events that require fast galectin-3 mobilization. <br/><br>
In the fourth paper we tested the inhibitory potential of a few plant products for several galectins. We found that their activity was very weak, hence the search for more potent anti-galectin, perhaps also anti-inflammatory remedies continues.},
  author       = {Lepur, Adriana},
  isbn         = {978-91-87189-31-9},
  issn         = {1652-8220},
  keyword      = {galectin-3,galectin-1,M1 macrophage,M2 macrophage,self-association,fluorescence anisotropy,citrus pectin,galactomannane},
  language     = {eng},
  pages        = {71},
  publisher    = {Department of Laboratory Medicine, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Functional properties of galectin-3. Beyond the sugar binding.},
  volume       = {2012:68},
  year         = {2012},
}