Comparative Neuroprotective Effects of Rasagiline and Aminoindan with Selegiline on Dexamethasone-Induced Brain Cell Apoptosis

Tazik, Shawna; Johnson, Shakevia; Lu, Deyin; Johnson, Chandra; Youdim, Moussa B. H.; Stockmeier, Craig A.; Ou, Xiao-Ming

doi:10.1007/s12640-009-9030-4

Cited by 47 publications

(38 citation statements)

References 42 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%

“…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. 1242-MG cells express reasonable levels of MAO B and show responses to glucocorticoids in terms of the activation of GR (Tazik et al, 2009). First, we determined the effect of glucocorticoids on MAO B catalytic activity.…”

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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“…(-)Deprenyl protected neuronal cells in cellular and animal models (Maruyama et al 1998;Kupsch et al 2001) and also showed disease modification in PD (Palhagen et al 2006). Rasagiline was reported to be more potent in protecting neuronal cells in cellular and animal models of evoked neuropathy than (-)deprenyl (Abu-Raya et al 2002;Tazik et al 2009). Also by clinical trials, rasagiline was proved to have a possible disease-modifying effect (Olanow et al 2009), even though the final conclusion for its neuroprotective effect of MAO-B inhibitors is still controversial (Riederer et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Type A monoamine oxidase is associated with induction of neuroprotective Bcl-2 by rasagiline, an inhibitor of type B monoamine oxidase

Inaba-Hasegawa¹,

Akao

Maruyama

et al. 2011

J Neural Transm

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Rasagiline and (-)deprenyl (selegiline), irreversible type B monoamine oxidase (MAO-B) inhibitors, protect neuronal cells through gene induction of pro-survival Bcl-2 and neurotrophic factors in the cellular models of neurodegenerative disorders. In this paper, the role of MAO in the up-regulation of neuroprotective Bcl-2 gene by these inhibitors was studied using type A MAO (MAO-A) expressing wild SH-SY5Y cells and the transfection-enforced MAO-B overexpressed cells. Rasagiline and (-)deprenyl, and also befloxatone, a reversible MAO-A inhibitor, increased Bcl-2 mRNA and protein in SH-SY5Y cells. Silencing MAO-A expression with short interfering (si) RNA suppressed Bcl-2 induction by rasagiline, but not by (-)deprenyl. MAO-B overexpression inhibited Bcl-2 induction by rasagiline and befloxatone, but did not affect that by (-)deprenyl, suggesting the different mechanisms behind Bcl-2 gene induction by these MAO-B inhibitors. The novel role of MAO-A in Bcl-2 induction by rasagiline is discussed with regard to the molecular mechanism underlying neuroprotection by the MAO inhibitors.

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“…Deprenyl is a selective inhibitor of monoamine oxidase type-B which is responsible for the oxidation of dopamine in the brain. MAO is an enzyme for the degradation of aminergic neurotransmitters; dopamine, noradrenaline and serotonin and dietary amines and MAO inhibitors are classical antidepressant drugs (Tazik et al 2009). Furthermore, by inducing antioxidant enzymes and decreasing the formation of reactive oxygen species, deprenyl is able to combat an oxidative challenge implicated as a common causative factor in neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Age-related protective effect of deprenyl on changes in the levels of diagnostic marker enzymes and antioxidant defense enzymes activities in cerebellar tissue in Wistar rats

Subramanian

James

2010

Cell Stress and Chaperones

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Antioxidants are free radical scavengers and protect living organisms against oxidative damage to tissues. Experimental evidence implicates oxygen-derived free radicals as important causative agents of aging and the present study was designed to evaluate the age-related effects of deprenyl on the antioxidant defense in the cerebellum of male Wistar rats. Experimental rats of three age groups (6, 12, and 18 months old) were administered with liquid deprenyl (2 mg/kg body weight/day for a period of 15 days i.p) and levels of diagnostic marker enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase) in plasma, lipid peroxides, reduced glutathione and activities of glutathione-dependent antioxidant enzymes (glutathione peroxidase and glutathione-S-transferase) and antiperoxidative enzymes (catalase and superoxide dismutase) in the cerebellar tissue were determined. Intraperitonial administration of deprenyl (2 mg/kg body weight/day for a period of 15 days) significantly (p<0.05) attenuated the agerelated alterations noted in the levels of diagnostic marker enzymes plasma of experimental animals. Deprenyl also exerted an antioxidant effect against aging process by hindering lipid peroxidation to an extent. Moderate rise in the levels of reduced glutathione and activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes was also observed. The results of the present investigation indicated that the protective potential of deprenyl was probably due to the increase of the activity of the free radical scavenging enzymes or to a counteraction of free radicals by its antioxidant nature or to a strengthening of neuronal membrane by its membrane-stabilizing action. Histopathological observations also confirmed the protective effect of deprenyl against the age-related aberrations in rat cerebellum. These data on the effect of deprenyl on parameters of normal aging provides new additional information concerning the anti-aging potential of deprenyl.

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Comparative Neuroprotective Effects of Rasagiline and Aminoindan with Selegiline on Dexamethasone-Induced Brain Cell Apoptosis

Cited by 47 publications

References 42 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

Type A monoamine oxidase is associated with induction of neuroprotective Bcl-2 by rasagiline, an inhibitor of type B monoamine oxidase

Age-related protective effect of deprenyl on changes in the levels of diagnostic marker enzymes and antioxidant defense enzymes activities in cerebellar tissue in Wistar rats

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