Trans-2-phenylcyclopropylamine induces nerve cells apoptosis in zebrafish mediated by depression of LSD1 activity
| Autor: | Song Hou-yan, Jiang Qiu, Zhang Jie, Tan Li, Hou Jia-Yun, Zen Ping-Yao |
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| Rok vydání: | 2009 |
| Předmět: |
animal structures
Morpholino Apoptosis In situ hybridization Demethylase activity medicine In Situ Nick-End Labeling Animals Humans In Situ Hybridization Zebrafish Neurons TUNEL assay biology Behavior Animal General Neuroscience Tranylcypromine Oxidoreductases N-Demethylating Oligonucleotides Antisense Zebrafish Proteins Molecular biology Antidepressive Agents Cell biology biology.protein Demethylase Signal transduction Tumor Suppressor Protein p53 Biomarkers medicine.drug Signal Transduction |
| Zdroj: | Brain research bulletin. 80(1-2) |
| ISSN: | 1873-2747 |
| Popis: | Trans -2-phenylcyclopropylamine (referred to as PCPA hereafter, also known as tranylcypromine and Parnate) is used clinically as an antidepressant. Here, we use a new model—zebrafish ( Danio rerio ) to study the molecular mechanisms of its adverse reactions in vivo . Following a PCPA exposure (75 μM), embryos showed “sluggish” action (slow swim and slow escape action). Whole mount in situ hybridization showed that sox1a and huc expressions were downregulated in PCPA-treated embryos, which indicated a decrease in the number of nerve cells. TUNEL assay diplayed that the drop of nerve cells number due to excessive apoptosis. Moreover, lysine-specific demethylase 1 morpholino injection (LSD1 MO) also induced increased cellular apoptosis in embryos just as PCPA. RT-PCR at 24 hpf evaluated that the absence of LSD1 resulted in increased expression of two p53 target genes (p21 and bax2). These findings demonstrate for the first time that PCPA-induced apoptosis through inhibition of LSD1 demethylase activity and p53-dependent signaling pathway might be required for the maintenance of nerve cell apoptosis. |
| Databáze: | OpenAIRE |
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