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

Autori
Lepur, Adriana

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Faculty of Medicine, Prirodoslovno-Matematicki Fakultet

Mjesto
Lund, Zagreb

Datum
05.10

Godina
2012

Stranica
70

Mentor
Hakon Leffler, Jerka Dumić

Ključne riječi
galectin-3; galectin-1; M1 macrophage; M2 macrophage; self-association; fluorescence anisotropy; citrus pectin; galactomannane

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA