Bastian Paulina, Dulski Jaroslaw, Roszmann Anna, Jacewicz Dagmara, Kuban-Jankowska Alicja, Slawek Jaroslaw, Wozniak Michal, Gorska-Ponikowska Magdalena
Department of Medical Chemistry, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland.
Department of Neurological-Psychiatric Nursing, Medical University of Gdansk, 80-211 Gdansk, Poland.
Antioxidants (Basel). 2021 Feb 6;10(2):248. doi: 10.3390/antiox10020248.
Mitochondria, as "power house of the cell", are crucial players in cell pathophysiology. Beyond adenosine triphosphate (ATP) production, they take part in a generation of reactive oxygen species (ROS), regulation of cell signaling and cell death. Dysregulation of mitochondrial dynamics may lead to cancers and neurodegeneration; however, the fusion/fission cycle allows mitochondria to adapt to metabolic needs of the cell. There are multiple data suggesting that disturbed mitochondrial homeostasis can lead to Parkinson's disease (PD) development. 2-methoxyestradiol (2-ME), metabolite of 17β-estradiol (E2) and potential anticancer agent, was demonstrated to inhibit cell growth of hippocampal HT22 cells by means of nitric oxide synthase (NOS) production and oxidative stress at both pharmacologically and also physiologically relevant concentrations. Moreover, 2-ME was suggested to inhibit mitochondrial biogenesis and to be a dynamic regulator. This review is a comprehensive discussion, from both scientific and clinical point of view, about the influence of 2-ME on mitochondria and its plausible role as a modulator of neuron survival.
线粒体作为“细胞的动力工厂”，在细胞病理生理学中起着关键作用。除了产生三磷酸腺苷（ATP）外，它们还参与活性氧（ROS）的生成、细胞信号传导的调节以及细胞死亡过程。线粒体动力学失调可能导致癌症和神经退行性疾病；然而，融合/裂变循环使线粒体能够适应细胞的代谢需求。有多项数据表明，线粒体稳态紊乱会导致帕金森病（PD）的发展。2-甲氧基雌二醇（2-ME）是17β-雌二醇（E2）的代谢产物，也是一种潜在的抗癌药物，在药理学和生理相关浓度下，均通过一氧化氮合酶（NOS）的产生和氧化应激来抑制海马HT22细胞的生长。此外，有研究表明2-ME可抑制线粒体生物合成，并且是一种动态调节剂。本综述从科学和临床角度全面讨论了2-ME对线粒体的影响及其作为神经元存活调节剂的潜在作用。
