Type B and A monoamine oxidase and their inhibitors regulate the gene expression of Bcl-2 and neurotrophic factors in human glioblastoma U118MG cells: different signal pathways for neuroprotection by selegiline and rasagiline

Type B and A monoamine oxidase and their inhibitors regulate the gene expression of Bcl-2 and... Type B monoamine oxidase (MAO-B) in glial cells has been considered to be associated with neuronal death in Parkinson’s disease. MAO-B inhibitors, rasagiline and selegiline [(−)deprenyl], protect neurons in animal and cellular models of neurodegeneration. However, the role of MAO-B itself in the regulation of cell death processing remains elusive, whereas type A MAO (MAO-A) mediates the induction of anti-apoptotic Bcl-2 genes by rasagiline and selegiline. In this paper, the involvement of MAOs in the induction of neuroprotective genes by MAO inhibitors was investigated in human glioblastoma U118MG cells expressing mainly MAO-B. Selegiline significantly increased Mao-B, which was suppressed by Mao-A knockdown with short interfering (si)RNA, whereas rasagiline less markedly increased Mao-B, which was not affected by Mao-A knockdown. Mao-A mRNA was also markedly increased by rasagiline and selegiline, and Mao-B knockdown significantly enhanced the induction by selegiline, but not by rasagiline. Mao-B knockdown also significantly increased mRNA levels of Bcl-2, brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Selegiline synergistically enhanced the expression of these genes in Mao-B knockdown cells, but Mao-A knockdown suppressed the increase. Rasagiline increased BDNF and GDNF, which Mao-B and Mao-A knockdown inhibited. These results show that MAO-B might function as a repressor and MAO-A as a mediator in the constitutional expression of pro-survival genes, and that MAO-B and MAO-A might regulate different signal pathways for rasagiline and selegiline to induce neuroprotective genes. The novel role of glial MAOs in the regulation of gene expression is discussed. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neural Transmission Springer Journals

Type B and A monoamine oxidase and their inhibitors regulate the gene expression of Bcl-2 and neurotrophic factors in human glioblastoma U118MG cells: different signal pathways for neuroprotection by selegiline and rasagiline

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/lp/springer_journal/type-b-and-a-monoamine-oxidase-and-their-inhibitors-regulate-the-gene-tlbKfV39rx
Publisher
Springer Vienna
Copyright
Copyright © 2017 by Springer-Verlag Wien
Subject
Medicine & Public Health; Neurology; Psychiatry; Pharmacology/Toxicology; Neurosciences
ISSN
0300-9564
eISSN
1435-1463
D.O.I.
10.1007/s00702-017-1740-9
Publisher site
See Article on Publisher Site

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