Monoamine oxidases A and B are differentially regulated by glucocorticoids and “aging” in human skin fibroblasts
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Two forms of monoamine oxidase (MAO A and MAO B) exist which, although similar in a number of properties, can be distinguished on the basis of their substrate specificity, inhibitor sensitivity, kinetic parameters, and protein structure. These properties were used to study the molecular mechanism(s) by which glucocorticoid hormones and “aging,” known to alter MAO activityin vivo, regulated the expression of MAO A and MAO B in cultured human skin fibroblasts.
The addition of dexamethasone or hydrocortisone to cultures resulted in a doseand time-dependent increase in total MAO activity, whereas the removal of hormone from cultures resulted in a time-dependent decrease in activity toward control levels.
The response to dexamethasone was affected by culture conditions such as serum concentration, feeding frequency, and cellular “age.”
Cellular aging, in the absence of hormone, also resulted in increased levels of total MAO activity.
The effects of hormones and aging on total MAO activity appeared to be selective for MAO A. The 6- to 14-fold increases in total activity were paralleled by similar increases in the activity and amount of active MAO A but less than 2- to 3-fold increases in the activity and amount of MAO B.
Altered synthesis or degradation of the active enzyme appeared to account for the effects of hormones, aging, and various culture conditions on MAO activity. Inhibitor sensitivity, substrate affinity, electrophoretic mobility, and molecular turnover number of either form of the enzyme were not altered during dexamethasone treatment or during cellular aging. However, rates of active MAO synthesis were affected by hormone treatment and feeding frequency, rates of active MAO degradation by serum concentration, and rates of active MAO synthesis or degradation by aging.
In summary, we have shown that glucocorticoids and cellular aging selectively affect the amount of MAO A at the level of active enzyme synthesis or degradation. Further, our finding that the expression of the two forms of MAO in human fibroblasts can be independently regulated supports the growing evidence that MAO A and MAO B are separate molecular entities.
Key wordsmonoamine oxidase glucocorticoids aging hormonal regulation isozymes human fibroblasts cell culture
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