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Biomedical subjects

C M Coughlan

Publications and source records attributed to C M Coughlan.

4 recordsLinked to original sources

Tissue-specific regulation of sialyltransferase activities in the rat by corticosteroids in vivo.

In this study we have examined the effects of corticosteroids on both the total sialyltransferase (sialyl-T) activity and on two individual isozymes in neural, hepatic, and renal tissues using an in vivo model system. Rats were adrenalectomised to deplete their endogenous stores of steroid hormones, and some subsequently received steroid replacement with dexamethasone or aldosterone. Adrenalectomy resulted in a significant decrease in total neural sialyl-T activity when compared with sham-operated animals in the four brain regions examined, indicating that total sialyl-T activity is normally under positive corticosteroid control. The subsequent effects of exogenous corticosteroids exhibited regional specificity with the enzyme activities in the cortex, cerebellum, and brainstem being stimulated by both dexamethasone and aldosterone and enzyme activity in the hippocampus being stimulated by aldosterone alone. In general, the changes in total enzyme activity could be attributed to the alpha 2,6 sialyl-T isozyme, although the changes in the cerebellum appeared to coincide with alpha 2,3 sialyl-T activity. In the liver, adrenalectomy resulted in an increase in enzyme activity which was not altered by administration of corticosteroids. There were no changes in total renal sialyl-T activity in any of the four experimental groups although certain changes were observed at the level of individual sialyl-T isozymes. These results demonstrate that sialyl-T activity in certain tissues is under the control of corticosteroids and that this is both a tissue-specific and region-specific effect.

Adrenal Cortex Hormones

The control of sialyltransferase activity in tumor-cell lines derived from different tissues in multifactorial.

The activities of the sialyltransferase enzymes and the resulting expression of sialoglycoproteins were examined in tumor cells derived from different tissues in order to gain a greater understanding of the factors controlling the cell glycosylation state. Cell-cell contact, which is dependent on cell confluency state, was shown to influence glycosylation in the neurally-derived mouse neuro-2A neuroblastoma and the C6 glioma cell lines. Both showed a relatively high level of cell sialyltransferase activity under sub-confluent conditions with activity decreasing upon the formation of cell-cell contacts associated with confluency. A parallel decrease in the expression of sialoglycoproteins, as determined by lectin blot analysis, was observed under these conditions. In contrast, the H411e hepatoma cell line showed an increase in enzyme activity with confluency with the susceptibility of the enzyme in this cell line to glucocorticoid induction only being detected in sub-confluent cell cultures. The number of trypsinisation cycles of the cells was also shown to affect the enzyme activity of the neuro-2A and C6 cells with an increase in enzyme activity coincident with passage number being observed in the neuro-2A cells, and a decrease in the C6 glioma cell line. Trypsinisation had no effect on enzyme activity in the H411e cells. These results demonstrate that the control of sialyltransferase activity in tumor cells is multifactorial with the tissue of origin playing a key role.

Animals

A decrease in serum sialyltransferase levels in Alzheimer's disease.

A reliable antemortem serum marker for Alzheimer's disease (AD) would be of great importance for the early detection and subsequent therapeutic management of the disease. We have noted a significant decrease in serum levels of the soluble form of the sialyltransferase enzyme in a group of AD patients when compared with both age-matched elderly (over 60 years) and young (under 60 years) controls. In a population of Down's syndrome patients, who develop AD pathology with increasing age, there was an age-related decrease in serum sialyltransferase activity in patients from 20 to 60 years to approach enzyme levels similar to those observed in the AD group. This significant decrease in serum sialyltransferase levels observed may both prove a useful peripheral early biochemical marker of neurodegeneration and provide an indication of the underlying cellular events that occur during the process of nerve cell death in AD.

Adult