Monoamine oxidase B expression is selectively regulated by dexamethasone in cultured rat astrocytes

Carlo, Pia; Violani, Elisabetta; Río, M. del; Olasmaa, Marjut; Santagati, Sabrina; Maggi, Adriana; Picotti, G. B.

doi:10.1016/0006-8993(95)01353-9

Cited by 31 publications

(13 citation statements)

References 46 publications

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“…1, MAO B catalytic activity increased by ϳ2.8-fold in response to dexamethasone (a potent synthetic glucocorticoid hormone, 100 nM, 48 h) in 1242-MG cells. This is consistent with the observations as reported by other groups using different neuronal/glial culture systems (Carlo et al, 1996;Tazik et al, 2009). The concentrations of dexamethasone as used under current experimental conditions did not produce cytotoxicity, which was ensured in our previous study (Ou et al, 2006a).…”

Section: Resultssupporting

confidence: 93%

“…The ability of glial cells to metabolize monoamine neurotransmitters has been firmly established; in fact, more than 90% of brain MAO is found extraneuronally (Oreland et al, 1983). MAO B is abundant in glial cells (Shih et al, 1999), and the interaction between glucocorticoids and MAO B has also been well defined in the glial culture system (Carlo et al, 1996). Hence, in this study, we used a human glioblastoma 1242-MG cell line as a model system to investigate the molecular mechanisms responsible for glucocorticoid activation of MAO B.…”

Section: Resultsmentioning

confidence: 99%

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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

Chen

Ou²,

Wu³

et al. 2010

Mol Pharmacol

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Glucocorticoid steroid hormones play important roles in many neurophysiological processes such as responses to stress, behavioral adaption, and mood. One mechanism by which glucocorticoids exert functions in the brain is via the modulation of neurotransmission systems. Glucocorticoids are capable of inducing the activities of monoamine oxidases (MAOs), which degrade monoamine neurotransmitters including serotonin, norepinephrine, phenylethylamine, and dopamine. However, the molecular mechanisms for such induction are not yet fully understood. Here, we report that dexamethasone, a synthetic glucocorticoid hormone, stimulates MAO B (an isoform of MAOs) promoter and catalytic activities via both the fourth glucocorticoid response element (GRE) and simian virus 40 promoter factor 1 (Sp1) binding sites in MAO B promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation analysis demonstrated that glucocorticoid receptor binds to the fourth GRE in vitro and in vivo. Using Sp1-binding motifs as bait in a yeast one-hybrid system, we identified two novel transcriptional repressors of MAO B, E2F-associated phosphoprotein (EAPP) and R1 (RAM2/CDCA7L/ JPO2), that down-regulate MAO B via MAO B core promoter, which contains Sp1 sites. EMSA suggested that EAPP and R1 competed with Sp1 for binding to the Sp1 site in vitro. Moreover, EAPP and R1 reduced Sp1-activated glucocorticoid activation of MAO B promoter. In response to dexamethasone, lower occupancy by EAPP and R1 and higher occupancy by Sp1 were shown at the natural MAO B core promoter. Together, this study uncovers for the first time the molecular mechanisms for glucocorticoid activation of MAO B gene and provides new insights into the hormonal regulation of MAO.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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

Chen

Ou²,

Wu³

et al. 2010

Mol Pharmacol

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“…Glucocorticoids selectively stimulated MAO-A activity in bovine adrenal endothelial cells by 1.5-to 2.5-fold (32). In rat astrocytes, dexamethasone increased mRNA and protein expression of MAO-B, which was inhibited by the GR inhibitor RU 486 (33), whereas in vivo studies showed overall decreases in young, but increases in older, rats of both MAO-A and -B activities (34,35).…”

Section: Discussionmentioning

confidence: 90%

Monoamine oxidase‐A is a major target gene for glucocorticoids in human skeletal muscle cells

Manoli

Alesci³

et al. 2005

FASEB j.

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Skeletal myopathy is a common complication of endogenous and exogenous glucocorticoid excess, yet its pathogenetic mechanisms remain unclear. There is accumulating evidence that mitochondrial dysfunction and oxidative stress are involved in this process. To explore the glucocorticoid-induced transcriptional adaptations that may affect mitochondrial function in skeletal muscle, we studied gene expression profiles in dexamethasone-treated primary human skeletal myocytes using a cDNA microarray, which contains 501 mitochondria-related genes. We found that monoamine oxidase A (MAO-A) was the most significantly up-regulated gene. MAO-A is the primary enzyme metabolizing catecholamines and dietary amines, and its role in skeletal muscle remains largely unexplored. Dexamethasone induced dose- and time-dependent increases of MAO-A gene and protein expression, while its effects on MAO-B were minimal. Both the glucocorticoid receptor (GR) and the Sp1 transcription factor were required for dexamethasone-induced MAO-A mRNA expression, as blockade of the GR with RU 486 or ablation of Sp1 binding with mithramycin abrogated MAO-A mRNA induction. The observed dexamethasone effect was biologically functional, as this steroid significantly increased MAO-mediated hydrogen peroxide production. We suggest that MAO-A-mediated oxidative stress can lead to cell damage, representing a novel pathogenetic mechanism for glucocorticoid-induced myopathy and a potential target for therapeutic intervention.

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“…9,11 On the other hand, in mammals the two promoters have different organizations and are thus subject to a different type of regulation. 34 Members of the RAR nuclear receptor family are detectable in the chick embryo early in its development.…”

Section: Discussionmentioning

confidence: 99%

Monoamine oxidase A and B activities in embryonic chick hepatocytes: differential regulation by retinoic acid

Nicotra¹,

Falasca²,

Senatori³

et al. 2001

Cell Biochemistry & Function

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Monoamine oxidases (MAOs) A and B are two isoenzymes involved in the degradation of many biological amines in the nervous system and in peripheral organs. In the present work hepatocytes isolated from 14-day-old chick embryos were used as a model system to determine whether retinoic acid (RA) is capable of modulating the activity of the two MAO forms. RA is a retinoid that, by binding with nuclear receptors, interferes with the expression of specific genes in many differentiation processes. Enzymic activity was measured with a radiochemical method using serotonin and beta-phenylethylamine as preferential substrates for MAO A and MAO B, respectively. The specific activity of the two forms was measured in hepatocytes cultured for 24, 48 and 72 h in the presence and the absence of serum. RA stimulated MAO B but not MAO A activity, in a dose- and time-dependent way, and only in the presence of serum. Maximum stimulation (about 3.5-fold) was obtained after treatment with 5 microM RA for 72 h. Kinetic analysis of MAO B activity showed an increase in V(max) in treated hepatocytes (5 microM RA for 72 h) with no change in K(m). In conclusion, the present work shows that RA selectively elicits MAO B activity in cultured chick embryonic hepatocytes, this stimulation requires the presence of some factors present in the serum and is probably due to an increase in the number of enzyme molecules.

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Monoamine oxidase B expression is selectively regulated by dexamethasone in cultured rat astrocytes

Cited by 31 publications

References 46 publications

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

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

Monoamine oxidase‐A is a major target gene for glucocorticoids in human skeletal muscle cells

Monoamine oxidase A and B activities in embryonic chick hepatocytes: differential regulation by retinoic acid

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