PMID- 28577058 OWN - NLM STAT- MEDLINE DCOM- 20190729 LR - 20190729 IS - 1435-1463 (Electronic) IS - 0300-9564 (Linking) VI - 124 IP - 9 DP - 2017 Sep TI - 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. PG - 1055-1066 LID - 10.1007/s00702-017-1740-9 [doi] AB - 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. FAU - Inaba-Hasegawa, Keiko AU - Inaba-Hasegawa K AD - Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan. FAU - Shamoto-Nagai, Masayo AU - Shamoto-Nagai M AD - Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan. FAU - Maruyama, Wakako AU - Maruyama W AD - Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan. FAU - Naoi, Makoto AU - Naoi M AD - Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan. mnaoi@dpc.agu.ac.jp. LA - eng PT - Journal Article DEP - 20170602 PL - Austria TA - J Neural Transm (Vienna) JT - Journal of neural transmission (Vienna, Austria : 1996) JID - 9702341 RN - 0 (Antineoplastic Agents) RN - 0 (Indans) RN - 0 (Monoamine Oxidase Inhibitors) RN - 0 (Nerve Growth Factors) RN - 0 (Neuroprotective Agents) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Messenger) RN - 003N66TS6T (rasagiline) RN - 2K1V7GP655 (Selegiline) RN - EC 1.4.3.4 (Monoamine Oxidase) MH - Antineoplastic Agents/pharmacology MH - Apoptosis/drug effects/physiology MH - Astrocytes/drug effects/enzymology MH - Cell Line, Tumor MH - Gene Expression Regulation, Neoplastic/drug effects MH - Gene Knockdown Techniques MH - Glioblastoma/*drug therapy/*enzymology MH - Humans MH - Indans/*pharmacology MH - Monoamine Oxidase/genetics/*metabolism MH - Monoamine Oxidase Inhibitors/pharmacology MH - Nerve Growth Factors/metabolism MH - Neuroprotection/drug effects/physiology MH - Neuroprotective Agents/*pharmacology MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - RNA, Messenger/metabolism MH - Selegiline/*pharmacology MH - Signal Transduction/drug effects OTO - NOTNLM OT - Bcl-2 OT - MAO-B inhibitor rasagiline-selegiline OT - Neuroprotective gene induction OT - Neurotrophic factors BDNF-GDNF OT - Type B and A monoamine oxidase EDAT- 2017/06/04 06:00 MHDA- 2019/07/30 06:00 CRDT- 2017/06/04 06:00 PHST- 2017/03/29 00:00 [received] PHST- 2017/05/30 00:00 [accepted] PHST- 2017/06/04 06:00 [pubmed] PHST- 2019/07/30 06:00 [medline] PHST- 2017/06/04 06:00 [entrez] AID - 10.1007/s00702-017-1740-9 [pii] AID - 10.1007/s00702-017-1740-9 [doi] PST - ppublish SO - J Neural Transm (Vienna). 2017 Sep;124(9):1055-1066. doi: 10.1007/s00702-017-1740-9. Epub 2017 Jun 2.