Monoamine oxidase gene transcription in human cell lines: Treatment with psychoactive drugs and ethanol

Ekblom, Jonas; Zhu, Qin-shi; Chen, K.; Shih, Jean C.

doi:10.1007/bf01271228

Cited by 13 publications

(25 citation statements)

References 25 publications

(26 reference statements)

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“…30 The specific characteristics of the human MAOB gene promoter have been described and several fragments have been investigated with reporter gene assays. 29,31 For example, the maximal promoter activity for MAOB has been observed for a 0.15-kb GC-rich sequence close to the first exon of the gene. 29 Since no nuclear material is conferred to the platelets when they are released from the megakaryocytes, direct analysis of transcriptional regulation of MAO-B in platelets is not possible.…”

Section: Transcriptional Regulation Of Trbc Maomentioning

confidence: 99%

Genetic mechanisms of behavior—don't forget about the transcription factors

et al. 2001

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Major changes in psychiatric phenotypes due to genetic factors are seldom the result of single gene polymorphisms, but more often the result of several genetic mechanisms. In this millennium article we discuss the notion that the expression of numerous candidate genes could be regulated by the same transcription factors, and that polymorphisms in transcription factor genes might explain some phenotypes. We describe recent results of studies on the biological marker thrombocyte monoamine oxidase (trbc MAO) and the transcription factor AP-2␤. Low levels of trbc MAO is associated with temperamental characteristics such as sensation seeking and impulsiveness, and the enzyme is genetically regulated by specific transcriptional mechanisms. Transcription factor AP-2␤ is important for the development of midbrain structures and AP-2␤ has several binding sites in the regulatory regions of genes encoding key proteins in the monoamine transmitter systems. We have recently shown AP-2␤ to be linked to personality, binge-eating disorder, treatment with antidepressant drugs, and also to trbc MAO. Regardless of whether transcriptions factors, such as AP-2␤, regulate the expression of eg, the number of monoamine neurons or a variety of candidate genes within the monoamine systems, or both, we would like to emphasize the role of transcription factors, besides polymorphisms in monoaminergic candidate genes, when explaining inter-individual differences in temperament and psychiatric vulnerability. Molecular Psychiatry (2001) 6, 503-510.

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Section: Transcriptional Regulation Of Trbc Maomentioning

confidence: 99%

Genetic mechanisms of behavior—don't forget about the transcription factors

et al. 2001

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“…Similar to GAPDH, the MAO B expression is increased by ethanol in brain cell lines. Previously, ethanol has been found to increase MAO B promoter activity and altered the transcription factors binding to the MAO B promoter in SH-SY5Y cells (Ekblom et al 1996), suggesting that ethanol may directly enhance the MAO B expression by induction of transcription factor(s). Recently, we found that ethanol significantly increased TIEG2 expression in SH-SY5Y cells (Lu et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Glyceraldehyde-3-Phosphate Dehydrogenase–Monoamine Oxidase B-Mediated Cell Death-Induced by Ethanol is Prevented by Rasagiline and 1-R-Aminoindan

Johnson

et al. 2009

Neurotox Res

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The inhibitors of monoamine oxidase B (MAO B) are effectively used as therapeutic drugs for neuropsychiatric and neurodegenerative diseases. However, their mechanism of action is not clear, since the neuroprotective effect of MAO B inhibitors is associated with the blockage of glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-death cascade, rather than the inhibition of MAO B. Here, we provide evidence that GAPDH potentiates the ethanol-induced activity of MAO B and brain cell toxicity. The levels of nuclear GAPDH and MAO B activity are significantly increased in brain-derived cell lines upon 75 mM ethanol-induced cell death. Over-expression of GAPDH in cells enhances ethanol-induced cell death, and also increases the ethanol-induced activation of MAO B. In contrast, the MAO B inhibitors rasagiline and selegiline (0.25 nM) and the rasagiline metabolite, 1-R-aminoindan (1 μM) decreases the ethanol-induced MAO B, prevents nuclear translocation of GAPDH and reduces cell death. In addition, GAPDH interacts with transforming growth factor-beta-inducible early gene (TIEG2), a transcriptional activator for MAO B, and this interaction is increased in the nucleus by ethanol but reduced by MAO B inhibitors and 1-R-aminoindan. Furthermore, silencing TIEG2 using RNAi significantly reduces GAPDH-induced MAO B upregulation and neurotoxicity. In summary, ethanol-induced cell death, attenuated by MAO NIH Public Access

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“…This novel GAPDH–MAO‐B pathway may be therapeutically useful in combating the neuronal harmful effects of alcohol, previously demonstrated to increase MAO‐B activity and promoter transcription activity (Carlsson et al. 1980; Ekblom et al. 1996).…”

Section: Neuroprotective Effects Of 1‐(r)‐aminoindan: Insights From Imentioning

confidence: 96%

“…Also, 1-(R)-aminoindan decreased the ethanol-induced MAO-B activity and expression, prevented nuclear translocation of GAPDH and reduced cell death in human glioblastoma U-118 MG cells and neuroblastoma SH-SY5Y cells (Ou et al 2009). This novel GAPDH-MAO-B pathway may be therapeutically useful in combating the neuronal harmful effects of alcohol, previously demonstrated to increase MAO-B activity and promoter transcription activity (Carlsson et al 1980;Ekblom et al 1996). Combination exposure studies indicated that 1-(R)-aminoindan not only did not interfere with the neuroprotective activities of rasagiline or selegiline in PC-12 cells deprived of serum and nerve growth factor, but also possessed neuroprotective activity by itself, on the contrary to the neurotoxic effects of L-methamphetamine (Bar-Am et al 2004a).…”

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confidence: 98%

The neuroprotective mechanism of 1‐(R)‐aminoindan, the major metabolite of the anti‐parkinsonian drug rasagiline

Bar-Am

Weinreb

Amit

et al. 2010

Journal of Neurochemistry

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J. Neurochem. (2010) 112, 1131–1137. Abstract The anti‐parkinsonian drug, rasagiline [N‐propargyl‐1‐(R)‐aminoindan; Azilect®], is a secondary cyclic benzylamine and indane derivative, which provides irreversible, potent monoamine oxidase‐B (MAO‐B) inhibition and possesses neuroprotective and neurorestorative activities. A prospective clinical trial has shown that rasagiline confers significant symptomatic improvement and demonstrated alterations in Parkinson’s disease progression. Rasagiline is primarily metabolized by hepatic cytochrome P‐450 to form its major metabolite, 1‐(R)‐aminoindan, a non‐amphetamine, weak reversible MAO‐B inhibitor compound. Recent studies indicated the potential neuroprotective effect of 1‐(R)‐aminoindan, suggesting that it may contribute to the overall neuroprotective and antiapoptotic effects of its parent compound, rasagiline. This review article briefly highlights the molecular mechanisms underlying the neuroprotective properties of the active metabolite of rasagiline, 1‐(R)‐aminoindan, supporting the valuable potential of rasagiline for disease modification.

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Monoamine oxidase gene transcription in human cell lines: Treatment with psychoactive drugs and ethanol

Cited by 13 publications

References 25 publications

Genetic mechanisms of behavior—don't forget about the transcription factors

Genetic mechanisms of behavior—don't forget about the transcription factors

Glyceraldehyde-3-Phosphate Dehydrogenase–Monoamine Oxidase B-Mediated Cell Death-Induced by Ethanol is Prevented by Rasagiline and 1-R-Aminoindan

The neuroprotective mechanism of 1‐(R)‐aminoindan, the major metabolite of the anti‐parkinsonian drug rasagiline

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