Department of Physiology, College of Oriental Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
Neurochem Res. 2012 Oct;37(10):2117-24. doi: 10.1007/s11064-012-0833-y. Epub 2012 Jul 5.
Phenelzine is a potent monoamine oxidase inhibitor that is used in patients with depression. It is also well known that nitric oxide (NO) synthase inhibitors show preclinical antidepressant-like properties, which suggests that NO is involved in the pathogenesis of depression. The purpose of this study was to determine if phenelzine affects the production of NO and tumor necrosis factor-alpha (TNF-α) in activated microglia cells. BV-2 microglia cells and primary microglia cells were cultured in DMEM and DMEM/F12 and then cells were treated with LPS or LPS plus phenelzine for 24 h. The culture medium was collected for determination of NO, TNF-α, and IL-6 and cells were harvested by lysis buffer for Western blot analysis. Phenelzine increased the lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS), as well as the release of TNF-α and IL-6 in BV-2 microglia cells. It is also confirmed that phenelzine increased the levels of NO, TNF-α and IL-6 in LPS-activated primary microglia cells. Phenelzine increased nuclear translocation of NF-κB by phosphorylation of IκB-α in LPS-activated microglia cells. These findings suggest that high doses of phenelzine could aggravate inflammatory responses in microglia cells that are mediated by NO and TNF-α.
苯乙肼是一种强效的单胺氧化酶抑制剂，用于治疗抑郁症患者。众所周知，一氧化氮（NO）合酶抑制剂具有临床前抗抑郁样特性，这表明 NO 参与了抑郁症的发病机制。本研究旨在确定苯乙肼是否会影响激活的小胶质细胞中 NO 和肿瘤坏死因子-α（TNF-α）的产生。将 BV-2 小胶质细胞和原代小胶质细胞在 DMEM 和 DMEM/F12 中培养，然后用 LPS 或 LPS 加苯乙肼处理 24 小时。收集培养基用于测定 NO、TNF-α 和 IL-6，并用裂解缓冲液收获细胞进行 Western blot 分析。苯乙肼增加了脂多糖（LPS）诱导的诱导型一氧化氮合酶（iNOS）的表达，以及 LPS 激活的 BV-2 小胶质细胞中 TNF-α 和 IL-6 的释放。还证实苯乙肼增加了 LPS 激活的原代小胶质细胞中 NO、TNF-α 和 IL-6 的水平。苯乙肼通过 LPS 激活的小胶质细胞中 IκB-α 的磷酸化增加了 NF-κB 的核易位。这些发现表明，高剂量的苯乙肼可能会加重由 NO 和 TNF-α 介导的小胶质细胞中的炎症反应。
