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Svein Olav Kolset

Publications and source records attributed to Svein Olav Kolset.

10 recordsLinked to original sources
PubMed2006

Effect of hyperglycemic condition on proteoglycan secretion in cultured human endothelial cells.

BACKGROUND: Proteoglycans (PGs) are important constituents of the plasma membrane and of the basement membrane supporting the endothelial cell layer. Changes in the amounts or the structures of PGs in the endothelium may affect important functions such as turnover of lipoproteins, filtration properties, and regulation of chemokines during inflammation, which are all relevant in diabetes. AIM OF THE STUDY: The purpose of this study was to investigate if hyperglycemic conditions would affect the biosynthesis and secretion of PGs in cultured primary human endothelial cells. METHODS: Primary human umbilical cord vein endothelial cells were established and cultured in vitro. The cells were cultured either in medium with low glucose (LG) (1 g/l) or high glucose (HG) (4.5 g/l). From day 3-4 cells were labeled with (35)S-sulfate for 24 h. (35)S-Labeled macromolecules (medium) were purified by gel chromatography, and isolated macromolecules were analyzed by gel chromatography after different types of treatment, electrophoresis, and immunoprecipitation. RESULTS: Lower levels of secreted PGs were found in human endothelial cells exposed to HG. The major part of the PGs released was of the heparan sulfate (HS) type, and immunoprecipitation experiments showed that one such PG was syndecan-1. However, there was no difference in the ratio between HS and chondroitin sulfate (CS) under the different experimental conditions. Further, the PGs expressed neither differ with regard to molecular size of the glycosaminoglycan (GAG) chains, nor were their polyanionic properties affected by the different experimental conditions. CONCLUSION: The results obtained suggest that treatment of primary human endothelial cells with hyperglycemia leads to a decrease in PG secretion in primary cultures of human endothelial cells.

Basement Membrane↗
PubMed2006

High glucose and Nepsilon-(carboxymethyl) lysine bovine serum albumin modulate release of matrix metalloproteinases in cultured human endothelial cells.

BACKGROUND: Hyperglycaemia may contribute to endothelial dysfunction. Disturbances in endothelial functions include changes in the extracellular matrix underneath the cells. This may result from altered biosynthesis of matrix molecules or from modified biosynthesis and secretion of enzymes involved in the turnover of extracellular matrix. One important class of such enzymes are the matrix metalloproteinases (MMPs). AIM OF THE STUDY: The aim of this study was to investigate whether the condition of high glucose concentration relevant both to diabetes type 1 and 2 and metabolic syndrome, would affect the synthesis and release of MMPs in human umbilical cord endothelial cells (HUVEC) in vitro. METHODS: The HUVEC were isolated and cultured in vitro. The cells were exposed to medium with either low glucose (LG, 1 g/l) or high glucose (HG, 4.5 g/l) or the advanced glycation end product (AGE) N(epsilon)-(carboxymethyl) lysine bovine serum albumin (CML-BSA), at a concentration of 10 microg/ml. The HUVEC-conditioned media were harvested and subjected to gelatin zymography and Western blotting. RESULTS: When HUVEC were incubated with HG or CML-BSA under serum free conditions a decreased secretion of pro MMP-2 was observed, both with gelatin zymography and Western blotting. The HUVEC also secreted MMP-9, but at lower levels, and effects of HG treatment were not significant. When HUVEC were stimulated with phorbol 12-myristate 13-acetate (PMA) secretion of pro MMP-2 was not increased, but the activation of pro MMP-2 into lower molecular forms increased, irrespective of culturing in LG, HG or CML-BSA. CONCLUSION: The HUVEC exposed to high glucose or AGE exhibit decreased secretion of MMP-2. These findings may be relevant in understanding the altered turnover of the endothelial extracellular matrix observed in the diabetic state.

Blotting, Western↗
PubMed2006

[Advanced glycation end products and hyperglycaemia].

Hyperglycaemia leads to increased formation and accumulation of advanced glycation end products, and these molecules play an important role in the development of micro- and macrovascular complications in diabetes. The formation of advanced glycation end products are complex reactions that take place both intra- and extracellularly. Advanced glycation end products affect gene regulation by binding to receptors, but can also modify proteins, DNA and lipids directly. The amount in serum and tissues depends upon several factors. The extent of hyperglycaemia is the main determining factor for levels of glycation products in the body, but the ability to break down and excrete these products in the urine is also important. The most effective way of preventing late complications in diabetes caused by glycation products is strict regulation of blood sugar levels. Drugs that inhibit advanced glycation end products could potentially be important in the prevention of late complications in diabetes, but this needs further investigation.

Atherosclerosis↗
PubMed2005

[Fetal nutrition and future health].

Fetal nutrition may permanently affect physiological properties of the new individual and hence the risk of future disease. Epidemiological studies indicate that fetal nutrition may significantly influence the risk of diabetes, cardiovascular disease, and cancer. Controlled animal studies show that even properties traditionally considered as exclusively genetic, like fur colour, may be modified by altered maternal nutrition. The expression "fetal programming" has been introduced to describe permanent effects of environmental conditions in fetal life. An important mechanism of fetal programming seems to be epigenetic regulation. One example of epigenetic regulation is methylation of the DNA base cytosine in promoter regions of some genes. DNA methylation will lead to decreased gene expression. Over the last two decades, marked changes in dietary habits and other life style features have taken place among young Norwegian women. This is particularly reflected in the increasing prevalence of obesity. Maternal weight and metabolic status is closely associated with the growth and development of the fetus. Thus, diet and physical activity become particularly important aspects of the health of young women.

Animals↗
PubMed2004

Intracellular proteoglycans.

Proteoglycans (PGs) are proteins with glycosaminoglycan chains, are ubiquitously expressed and have a wide range of functions. PGs in the extracellular matrix and on the cell surface have been the subject of extensive structural and functional studies. Less attention has so far been given to PGs located in intracellular compartments, although several reports suggest that these have biological functions in storage granules, the nucleus and other intracellular organelles. The purpose of this review is, therefore, to present some of these studies and to discuss possible functions linked to PGs located in different intracellular compartments. Reference will be made to publications relevant for the topics we present. It is beyond the scope of this review to cover all publications on PGs in intracellular locations.

Animals↗
PubMed2003

[Glycaemic index].

Glycaemic index is a measure of blood glucose increase two hours after intake of food containing 50 g of carbohydrate. The reference is measurements after intake of 50 g glucose or white bread containing 50 g carbohydrate, which is set to the value of 100. The glycaemic index was developed to help persons with diabetes improve their blood glucose control in order to avoid long-term complications. Apple can have an index of approximately 40, while a baguette has 95 and pumpernickel bread 41. Some observational studies suggest that a carbohydrate diet with low glycaemic index may reduce the risk of overweight, diabetes type 2 and colon cancer. There are at present few published controlled clinical trials supporting this conclusion. The food industry and some people working with weight reduction have shown interest in using the glycaemic index. The system may easily cause confusion and leave the impression that important and nutritious carbohydrate-containing foods should be avoided. The glycaemic index could be a tool for dieticians and physicians counselling persons with metabolic syndrome, overweight, diabetes type 1 or 2.

Diabetes Mellitus↗
PubMed2002

Sulfation in the Golgi lumen of Madin-Darby canine kidney cells is inhibited by brefeldin A and depends on a factor present in the cytoplasm and on Golgi membranes.

Madin-Darby canine kidney cells are more resistant than most other cell types to the classical effects of brefeldin A (BFA) treatment, the induction of retrograde transport of Golgi cisternae components to the endoplasmic reticulum. Here we show that sulfation of heparan sulfate proteoglycans (HSPGs), chondroitin sulfate proteoglycans (CSPGs), and proteins in the Golgi apparatus is dramatically reduced by low concentrations of BFA in which Golgi morphology is unaffected and secretion still takes place. BFA treatment seems to reduce sulfation by inhibition of the uptake of adenosine 3'-phosphate 5'-phosphosulfate (PAPS) into the Golgi lumen, and the inhibitory effect of BFA was similar for HSPGs, CSPGs, and proteins. This was different from the effect of chlorate, a well known inhibitor of PAPS synthesis in the cytoplasm. Low concentrations of chlorate (2-5 mm) inhibited sulfation of CSPGs and proteins only, whereas higher concentrations (15-30 mm) were required to inhibit sulfation of HSPGs. Golgi fractions pretreated with BFA had a reduced capacity for the synthesis of glycosaminoglycans (GAGs), but control level capacity could be restored by the addition of cytosol from various sources. This indicates that the PAPS pathway to the Golgi lumen depends on a BFA-sensitive factor that is present both on Golgi membranes and in the cytoplasm.

Animals↗
PubMed2002

Effect of brefeldin A on heparan sulphate biosynthesis in Madin-Darby canine kidney cells.

Brefeldin A (BFA) perturbs the organization of the Golgi apparatus, such that Golgi stack components are fused with the endoplasmic reticulum (ER) and separated from the trans-Golgi network. In many cell types, BFA blocks the secretion of macromolecules but still allows the action of Golgi enzymes in the ER. Treatment of cells with BFA has been reported to inhibit the secretion of heparan sulphate (HS) proteoglycans and alter the structure of their HS components, but the nature of such structural alterations has not been characterized in detail. We analysed the effect of BFA on HS biosynthesis in Madin-Darby canine kidney (MDCK) cells, in which the Golgi complex is more resistant towards BFA than in most other cell types. We found that MDCK cells were able to secrete HS proteoglycans in spite of BFA treatment. However, the secretion of HS was reduced and the secreted HS differed from that produced by untreated cells. In BFA-treated cells, two structurally distinct pools of HS were generated. One pool was similar to HS from control cells, with the exception that the 6-O-sulphation of glucosamine (GlcN) residues was reduced. In contrast, the other pool consisted of largely unmodified N-acetylheparosan polymers with a low (<20%) proportion of N-sulphated GlcN residues but a substantial proportion of N-unsubstituted GlcN units, indicating that it had been acted upon by N-deacetylases and partly by the N-sulphotransferases, but not by O-sulphotransferases. Together, these findings represent a previously unrecognized alteration in HS biosynthesis caused by BFA, and differ dramatically from our previous findings in MDCK cells pertaining to the undersulphation of HS caused by sodium chlorate treatment.

Animals↗