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C M Coughlan

Publications and source records attributed to C M Coughlan.

8 recordsLinked to original sources
PubMed1998

Glucocorticoid induction of the alpha2,6 sialyltransferase enzyme in a mouse neural cell line.

Combined sialyltransferase (ST) activities were induced in the HN9 hippocampal cell line following treatment with the synthetic glucocorticoid dexamethasone (dex) for 24 hr. Induction occurred in a dose-dependent manner, with the maximum induction of a 2-fold increase over control enzyme levels occurring at a concentration of 10(-8) M dex. A minimum of 6 hr pretreatment with drug was required before significant induction could be detected and elevated enzyme levels persisted for up to 48 hr post-treatment. The induced form of the enzyme showed an increase in reaction maximum velocity (Vmax) while showing no change in affinity (Km) for the acceptor substrate asialofetuin. The alpha2,6 ST enzyme was demonstrated to be the primary enzyme induced and there was no change in expression of the alpha2,3 ST enzyme. Lectin blot analysis demonstrated an increase in the levels of the alpha2,6-linked cellular sialoglycoproteins and a parallel decrease in the alpha2,3 sialoglycoprotein levels.

Animals↗
PubMed1998

The effect of corticosteroids on serum sialyltransferase enzyme activities in the rat.

Previous studies have demonstrated corticosteroid regulation of sialyltransferase (sialyl-T) enzyme activities in a number of different tissues throughout the body. In this study we examined the regulatory effect of corticosteroids on serum enzyme activity in the rat. The total serum sialyl-T activity was not affected by a decrease in corticosteroid levels following adrenalectomy. However, while there was a significant increase in enzyme activity following dexamethasone treatment, aldosterone had no effect on this parameter. Subsequent examination of individual sialyl-T enzymes demonstrated a slight decrease in alpha2,6 sialyl-T activity following adrenalectomy which was restored to basal levels following dexamethasone treatment. The activity of the alpha2,3 sialyl-T enzyme was not affected by adrenalectomy or dexamethasone treatment, but was stimulated significantly by aldosterone. In general, the levels of serum sialoglycoproteins mirrored well the activities of the appropriate sialyl-T enzymes. These results demonstrate that serum sialyltransferase activity in the rat is under the influence of circulating corticosteroids.

Adrenal Cortex Hormones↗
PubMed1998

The role of glycoproteins in neural development function, and disease.

Glycoproteins play key roles in the development, structuring, and subsequent functioning of the nervous system. However, the complex glycosylation process is a critical component in the biosynthesis of CNS glycoproteins that may be susceptible to the actions of toxicological agents or may be altered by genetic defects. This review will provide an outline of the complexity of this glycosylation process and of some of the key neural glycoproteins that play particular roles in neural development and in synaptic plasticity in the mature CNS. Finally, the potential of glycoproteins as targets for CNS disorders will be discussed.

Animals↗
PubMed1997

The biochemical consequences of alpha2,6(N) sialyltransferase induction by dexamethasone on sialoglycoprotein expression in the rat H411e hepatoma cell line.

Previous studies have demonstrated sialyltransferase (ST) enzyme activity to be induced in hepatic cells by corticosteroids. In this study, we used the H411e rat hepatoma cell line to further characterise this induction with particular reference to the subsequent changes in the pattern of sialoglycoprotein (SGP) expression. The induction of total ST activity by dexamethasone was concentration dependent with maximum induction occurring 12 h subsequent to drug addition. Western blot analysis demonstrated that the induction was associated with an increase in the expression of the alpha2,6(N) ST enzyme with no change in the expression levels of the alpha2,3(N) enzyme. While the induction resulted in an increase in the reaction velocity (Vmax) of the enzyme for both the sugar donor (CMP-Neu5Ac) and the asialofetuin acceptor protein, there was no significant change in the enzyme affinity (Km) for the substrates, suggestive of either an increase in the expression or efficiency of the existing enzyme(s) rather than an induction of novel ST enzymes. Lectin blot analysis of cellular glycoprotein expression demonstrated no change in the expression patterns of either alpha2,3 or alpha2,6-linked SGP following enzyme induction. These results suggest that the available acceptor sites for the terminal sialic acid group(s) may be fully occupied in the control cells and therefore there are no further sites onto which the sialic acid can be transferred following induction of ST enzyme activity. This may be due to the high basal enzyme levels in the control cells already exhausting endogenous acceptor sites.

Animals↗
PubMed1996

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↗
PubMed1995

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↗
PubMedDate not supplied

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↗