Activation of Human Monoamine Oxidase B Gene Expression by a Protein Kinase C MAPK Signal Transduction Pathway Involves c-Jun and Egr-1

Wong, Wai Keong; Ou, Xiao-Ming; Chen, Kevin; Shih, Jean C.

doi:10.1074/jbc.m202844200

Cited by 71 publications

(53 citation statements)

References 39 publications

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“…The lysates were centrifuged at 4°C at 16,000 ϫ g for 20 min, and the supernatant was analyzed by Western blotting. Subcellular fractionation studies were performed as described previously (Wong et al, 2002), with minor modifications. Briefly, PBS-washed neuronal cultures were harvested by scraping in 200 l cold-buffer A (20 mM HEPES, pH 7.9, 400 mM NaCl, 1 mM MgCl 2 , 0.1 mM EDTA, 15% glycerol, 0.1 mM Na 3 VO 4 , 50 mM NaF, 1 mM DTT, 0.5 mM PMSF, and protease inhibitors).…”

Section: Methodsmentioning

confidence: 99%

Activation of Group III Metabotropic Glutamate Receptors Attenuates Rotenone Toxicity on Dopaminergic Neurons through a Microtubule-Dependent Mechanism

Jiang¹,

Yan²,

Feng³

2006

J. Neurosci.

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Section: Methodsmentioning

confidence: 99%

Activation of Group III Metabotropic Glutamate Receptors Attenuates Rotenone Toxicity on Dopaminergic Neurons through a Microtubule-Dependent Mechanism

Jiang¹,

Yan²,

Feng³

2006

J. Neurosci.

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“…8) was cotransfected with or without c-MycER, and the expression of R1 mRNA levels was determined. The result shows that the induction of R1 mRNA by c-MycER was further increased by inhibiting p38 MAPK (by overexpression of p38-AGF) in a concentration-dependent manner as shown in Fig.…”

Section: In the Presence Of Serum R1 Knockdown Decreases Cell Prolifementioning

confidence: 99%

Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway

Ou¹,

Chen²,

Shih

2006

Proc. Natl. Acad. Sci. U.S.A.

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Monoamine oxidase A (MAO A) degrades serotonin, norepinephrine, and dopamine and produces reactive oxygen that may cause neuronal cell death. We have previously reported that a novel transcription factor R1 (RAM2͞CDCA7L͞JPO2) inhibits the MAO A promoter and enzymatic activities. This study reports the roles of MAO A and R1 in apoptosis and proliferation. We have found that in serum starvation-induced apoptosis, p38 kinase, MAO A, and caspase-3 were increased, whereas Bcl-2 and R1 were reduced. Using a p38 kinase inhibitor, R1 overexpression, and MAO A inhibitor, we have shown that MAO A and R1 are downstream of p38 kinase and Bcl-2, but upstream of caspase-3. Inhibition of MAO A prevents cell apoptosis. This notion was further supported by the finding that serum starvation-induced apoptosis is reduced in cortical brain cells from MAO A-deficient mice compared with WT. In addition, we found that MAO A and R1 are involved in the c-Myc-induced proliferative signaling pathway in the presence of serum. Immunoprecipitation and immunohistochemistry experiments indicate that the oncogene c-Myc colocalizes with R1 and induces R1 gene expression. Using R1 overexpression, R1 small interfering RNA, and a MAO A inhibitor, we found that R1 and MAO A act upstream of cyclin D1 and E2F1. In summary, this study demonstrates the functions of MAO A and its repressor R1 in apoptotic signaling pathways.c-Myc ͉ caspase-3 ͉ p38 kinase ͉ proliferation ͉ transcription factor M onoamine oxidases (MAOs) A and B, located on the outer mitochondria membrane with a 70% amino acid sequence identity (1, 2), catalyze the oxidative deamination of biogenic and dietary amines including monoamine neurotransmitters serotonin, norepinephrine, dopamine, and phenylethylamine. MAO plays important roles in several psychiatric and neurological disorders (3). MAO exists in two forms, MAO A and MAO B. Their catalytic activity generates H 2 O 2 and nitrogen species, which are toxic products and may cause oxidative damage to mtDNA and have potential implications for apoptosis, aging, and neurodegenerative processes (4).The in vivo function of MAO A and MAO B has been studied extensively in MAO A and MAO B knockout (KO) mice (5-7). The regulation of MAO A and MAO B gene expression by extracellular stimulation, phorbol 12-myristate 13-acetate (PMA), has also been examined. PMA selectively increases MAO B but not MAO A gene expression by activation of protein kinase C and mitogen-activated protein kinase (MAPK) signaling pathways (8).Ample evidence has indicated an important role for MAO A in apoptosis. MAO A expression has been shown to increase after the depletion of neurotrophic factor mediated by p38 kinase in PC12 cells (9). A MAO A inhibitor, clorgyline, was able to protect cells from apoptosis induced by serum starvation in human melanoma m14 cells (10). More recently, MAO A has been found to be a target of a dopaminergic neurotoxin, N-methyl-(R)-salsolinol, which leads to apoptosis in a human neuroblastoma SH-SY5Y cell line (11). This apoptotic activity co...

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“…An Sp1-like transcription factor, transforming growth factor-␤-inducible early gene, also activates the MAO B promoter via overlapping Sp1 sites (12). The expression of MAO B is regulated by protein kinase C and the MAPK signaling pathway (13).…”

mentioning

confidence: 99%

Glucocorticoid and Androgen Activation of Monoamine Oxidase A Is Regulated Differently by R1 and Sp1

Chen

Shih

2006

Journal of Biological Chemistry

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145

123

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Monoamine oxidase (MAO)A Monoamine oxidase (MAO)2 is located on outer membranes of mitochondria in neuronal, glial, and other cells. It catalyzes the oxidative deamination of monoamine neurotransmitters such as serotonin, norepinephrine, dopamine, and phenylethylamine (1). MAO exists in two isoforms, MAO A and MAO B. MAO A preferentially oxidizes serotonin (5-hydroxytryptamine), norepinephrine, and dopamine and is irreversibly inhibited by low concentration of clorgyline (2). MAO B preferentially oxidizes phenylethylamine and benzylamine and is irreversibly inactivated by low concentrations of pargyline and deprenyl (3). MAO A and B are coded by different genes (4) closely linked on the X chromosome, Xp11.2-11.4 (5). Both genes consist of 15 exons with identical exonintron organization (6) and both are regulated by Sp1 factors; however, there are some differences in their cis-elements (7-9). The core promoter of MAO A consists of Sp1-binding sites that are activated by Sp1 (7) and repressed by a novel repressor R1 (RAM2/CDCA7L) (8). This core promoter has bi-directional activity (7). In addition, a functional polymorphism of a 30-bp repeat sequence has been identified and located ϳ1.2 kb upstream of the MAO A translation start site (10). The human MAO B promoter contains two clusters of overlapping Sp1 sites separated by a CACCC element (11). An Sp1-like transcription factor, transforming growth factor-␤-inducible early gene, also activates the MAO B promoter via overlapping Sp1 sites (12). The expression of MAO B is regulated by protein kinase C and the MAPK signaling pathway (13).A mutation in the human MAO A gene, which results in no enzymatic activity, is associated with aggressive behavior in males in a Dutch family (14). MAO A knock-out (KO) mice showed aggressive behavior in males (15), but MAO B KO mice did not show aggressive behavior (16). Interestingly, a spontaneous mutation of the MAO A gene in MAO B KO mice resulted in MAO A/B double KO mice, which showed hyperreactivity and anxiety-like behavior (12).Steroid hormones are involved in the regulation of many functions in which MAO also plays an important roles such as response to stress, behavioral adaptation and mood (17). Significant hypersecretion of glucocorticoids has been shown to be associated with depression (18). The synthetic glucocorticoid, dexamethasone, increases MAO A activity in human fibroblasts (19) and rat brain frontal cortex (20). Both anti-glucocorticoid agents (21) and MAO A inhibitors (22, 23) have been used in the treatment of depression. Androgens have also been shown to increase MAO activity in the rat brain (24).The biological action of glucocorticoids and androgens are mediated through their respective receptors, glucocorticoid receptor (GR) and androgen receptor (AR). GR and AR bind to derivatives of a common response element, i.e. the consensus glucocorticoid response element (GRE), 5Ј-GGTACAnnn-

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Activation of Human Monoamine Oxidase B Gene Expression by a Protein Kinase C MAPK Signal Transduction Pathway Involves c-Jun and Egr-1

Cited by 71 publications

References 39 publications

Activation of Group III Metabotropic Glutamate Receptors Attenuates Rotenone Toxicity on Dopaminergic Neurons through a Microtubule-Dependent Mechanism

Activation of Group III Metabotropic Glutamate Receptors Attenuates Rotenone Toxicity on Dopaminergic Neurons through a Microtubule-Dependent Mechanism

Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway

Glucocorticoid and Androgen Activation of Monoamine Oxidase A Is Regulated Differently by R1 and Sp1

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