| 1. |
- Agardh, Carl-David, et al.
(författare)
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Glutathione levels are reduced in diabetic rat retina but are not influenced by ischemia followed by recirculation
- 1998
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Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 47:3, s. 269-272
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals have recently been proposed to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the abnormal metabolism caused by diabetes and by ischemia followed by recirculation interferes with a free radical enzyme defense system in the retina, ie, glutathione. Diabetes mellitus was induced by injecting streptozotocin ([STZ] 60 mg/kg body weight [BW] intraperitoneally). After 2 and 6 months, respectively, glutathione levels were measured in the retina and compared against those of age-matched normal control rats. Retinal ischemia was induced by careful ligation of the vessels and the accompanying optic nerve behind the left eye bulb. The right eye served as a control. After 90 minutes of ischemia, retinal circulation was reestablished by removing the ligature. Two-month-old diabetic rats were kept for an additional 3 days and normal rats for 5 minutes, 15 minutes, or 3 days before they were killed for measurement of glutathione. Retinal levels of glutathione were significantly lower in 6-month diabetic compared with 2-month diabetic rats (16.6 +/- 2.9 v 19.0 +/- 2.2 nmol/mg protein, P < .05) and 6-month normal control rats (16.6 +/- 2.9 v 21.0 +/- 2.1 nmol/mg protein, P < .001). Ischemia followed by recirculation did not influence the total tissue level of glutathione either in 2-month-old diabetic rats or in normal rats. The present study indicates that the abnormal metabolism caused by diabetes, rather than by changes in retinal circulation, results in an impaired defense mechanism against free radicals, a factor that may be of importance for the development of diabetic retinopathy. However, since glutathione levels in the present study were measured in the whole retina, it cannot be excluded that particular cell types, such as vascular cells, show an alteration in glutathione that is masked by the glutathione levels in the other nonvascular cells of the retina. Studies using other techniques are needed to further explore this subject.
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| 2. |
- Agardh, Carl-David, et al.
(författare)
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The glutathione levels are reduced in Goto-Kakizaki rat retina, but are not influenced by aminoguanidine treatment
- 1998
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 17:3, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the levels of the free radical protecting enzyme glutathione and the endothelial/pericyte ratio in retinal capillaries in the Goto-Kakizaki (GK) Wistar rat, with and without aminoguanidine treatment. METHODS: Eight-month-old GK rats, with non-obese, spontaneous non-insulin-dependent diabetes mellitus (NIDDM), were examined after a six month period of aminoguanidine treatment. Glutathione levels were measured with high performance liquid chromatography and the endothelial/pericyte ratio was calculated in trypsin digested vessel preparations. RESULTS: The levels of glutathione in GK rat retina were significantly lower compared to controls (p = 0.0108). There was no difference in the endothelial/pericyte ratio compared to matched control rats (1.8 +/- 0.2 vs. 1.8 +/- 0.1, respectively). Aminoguanidine treatment did not influence either the degree of hyperglycemia, the levels of glutathione or the endothelial/pericyte ratio in GK or control rat retina. CONCLUSIONS: The results indicate that impaired glucose metabolism may influence one of the defense mechanisms for oxidative stress, but also suggest that decreased glutathione levels occur prior to morphological signs of pericyte loss and/or endothelial cell proliferation in this animal model of hereditary NIDDM.
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| 3. |
- Leffler, Hakon, et al.
(författare)
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Introduction to galectins.
- 2002
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Ingår i: Glycoconjugate Journal. - 1573-4986. ; 19:7-9, s. 433-440
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Stowell, Sean R., et al.
(författare)
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Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion
- 2008
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Ingår i: Journal of Immunology. - 1550-6606. ; 180:5, s. 3091-3102
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-1 (Gal-1) and galectin-3 (Gal-3) exhibit profound but unique immunomodulatory activities in animals but their molecular mechanisms are incompletely understood. Early studies suggested that Gal-1 inhibits leukocyte function by inducing apoptotic cell death and removal, but recent studies show that some galectins induce exposure of the common death signal phosphatidylserine (PS) independently of apoptosis. In tfhis study, we report that Gal-3, but not Gal-1, induces both PS exposure and apoptosis in primary activated human T cells, whereas both Gal-1 and Gal-3 induce PS exposure in neutrophils in the absence of cell death. Gal-1 and Gal-3 bind differently to the surfaces of T cells and only Gal-3 mobilizes intracellular Ca2+ in these cells, although Gal-1 and Gal-3 bind their respective T cell ligands with similar affinities. Although Gal-1 does not alter T cell viability, it induces IL-10 production and attenuates IFN-gamma production in activated T cells, suggesting a mechanism for Gal-1-mediated immunosuppression in vivo. These studies demonstrate that Gal-1 and Gal-3 induce differential responses in T cells and neutrophils, and identify the first factor, Gal-3, capable of inducing PS exposure with or without accompanying apoptosis in different leukocytes, thus providing a possible mechanism for galectin-mediated immunomodulation in vivo.
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| 5. |
- Sörme, Pernilla, et al.
(författare)
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Low micromolar inhibitors of galectin-3 based on 3'-derivatization of N-acetyllactosamine.
- 2002
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Ingår i: ChemBioChem. - 1439-4227. ; 3:2-3, s. 183-189
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Tidskriftsartikel (refereegranskat)abstract
- A strategy for generating potential galectin inhibitors was devised based on derivatization at the C-3′ atom in 3′-amino-N-acetyllactosamine by using structural knowledge of the galectin carbohydrate recognition site. A collection of 12 compounds was prepared by N-acylations or N-sulfonylations. Hydrophobic tagging of the O-3 atom in the N-acetylglucosamine residue with a stearic ester allowed rapid and simple product purification. The compounds were screened in a galectin-3 binding assay and three compounds with significantly higher inhibitory activities compared to the parent N-acetyllactosaminide were found. These three best inhibitors all carried an aromatic amide at the C-3′ position of the galactose moiety, which indicates that favorable interactions were formed between the aromatic group and galectin-3. The best inhibitor had an IC50 value (4.4 μM) about 50 times better than the parent N-acetyllactosaminide, which implies that it has potential as a valuable tool for studying galectin-3 biological functions and also as a lead compound for the development of galectin-3-blocking pharmaceuticals.
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