Monoamine oxidases A and B are differentially regulated by glucocorticoids and ?aging? in human skin fibroblasts

Abstract

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 activity in 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 dose- and 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.

Monoamine oxidase‐A is a novel driver of stress‐induced premature senescence through inhibition of parkin‐mediated mitophagy

“…This could have particular relevance in cardiac ageing, where MAO‐A is likely to be chronically activated due to: (a) sympathetic activation and enhanced release of norepinephrine from adrenergic nerves (Santulli & Iaccarino, 2016); and (b) overexpression of MAO‐A in the ageing heart (as shown in Figure 1a,b) or in age‐associated cardiac diseases (Manni et al, 2016; Villeneuve et al, 2013). In addition, the role of MAO‐A in senescence could be extended to different cell types, since MAO‐A has been characterized in many proliferative cells, such as fibroblasts and bone marrow mesenchymal stem cells, where its expression was significantly increased during ageing (Edelstein & Breakefield, 1986; Trouche et al, 2010). …”

Relationship of Monoamine Oxidase-A Distribution Volume to Postpartum Depression and Postpartum Crying

“…Given the functions of MAO-A, the present study argues that several types of processes that contribute to pathological mood are enhanced in PPD. MAO-A V T is an index of MAO-A level (Tong et al, 2013;Ginovart et al, 2006) and the changes in latter are strongly implicated in the effects of hormonal influences on the MAO-A activity (Nelson et al, 1979;Edelstein and Breakefield, 1986;Saura et al, 1992;Ma et al, 1993;Smith et al, 2004). MAO-A metabolizes monoamines such as serotonin, norepinephrine, and dopamine, creates reactive oxygen species such as hydrogen peroxide (H 2 O 2 ), thereby promoting a pro-oxidant state (Youdim et al, 2006), suggesting that enhanced monoamine metabolism and a pro-oxidant state may be present during PPD.…”

Transcription Factor E2F-Associated Phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and Simian Virus 40 Promoter Factor 1 (Sp1) Cooperatively Regulate Glucocorticoid Activation of Monoamine Oxidase B

“…Significant hypersecretion of glucocorticoids has been associated with depression (Duval et al, 2006), and antiglucocorticoid agents have been used in the treatment of depression (Wolkowitz and Reus, 1999). Dexamethasone, a potent synthetic glucocorticoid hormone, has been reported to increase both MAO A and MAO B activity in vitro (Edelstein and Breakefield, 1986) and in vivo (Slotkin et al, 1998). Glucocorticoids exert their effects by activating glucocorticoid receptor (GR) to bind to glucocorticoid response element (GRE) 5Ј-AGAACANNNTG-TACC-3Ј ("N" is any nucleotide) and to regulate the transcription of target genes (Wang and Hodgetts, 1998;Adcock et al, 2004).…”