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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

  • Translational Neurosciences - Original Article
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Abstract

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.

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Abbreviations

MAO-A and MAO-B:

Type A and B monoamine oxidase

MAOB-SH cells:

MAO-B overexpressed SH-SY5Y cells

siRNA:

Short interfering RNA

siMao-A and siMao-B :

siRNA against Mao-A and Mao-B

siNS :

Non-specific siRNA

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Authors and Affiliations

  1. Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan

    Keiko Inaba-Hasegawa, Masayo Shamoto-Nagai, Wakako Maruyama & Makoto Naoi

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  1. Keiko Inaba-Hasegawa
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  2. Masayo Shamoto-Nagai
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  3. Wakako Maruyama
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  4. Makoto Naoi
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Correspondence to Makoto Naoi.

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Inaba-Hasegawa, K., Shamoto-Nagai, M., Maruyama, W. et al. 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. J Neural Transm 124, 1055–1066 (2017). https://doi.org/10.1007/s00702-017-1740-9

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  • DOI: https://doi.org/10.1007/s00702-017-1740-9

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