Asymmetric dimethylarginine (ADMA) is a well-known endogenous nitric oxide synthase (NOS) inhibitor. Although it has been shown to be a novel risk marker in cardiovascular medicine and chronic kidney disease, we speculated that in some states associated with excess of nitric oxide (NO), such as 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neuronal injury, ADMA might be protective by limiting the toxic effect of high concentrations of NO. 2. The aim of the present study is to explore the protection of ADMA against MPP(+)-induced apoptosis and the molecular mechanisms underlying in PC12 cells. 3. We found that exogenous application of ADMA obviously protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by reducing the loss of mitochondrial membrane potential, but also by attenuating an increase in intracellular reactive oxygen species. Moreover, ADMA attenuated MPP(+)-induced excessive activation of nitric oxide synthase and overproduction of NO. 4. The results of the present study suggest that the protection caused by ADMA is related to preserving mitochondrial membrane potential and attenuating the MPP(+)-induced intracellular reactive oxygen species generation through inhibiting nitric oxide synthase activity and limiting NO generation.
摘要
不对称二甲基精氨酸（ADMA）是一种众所周知的内源性一氧化氮合酶（NOS）抑制剂。尽管它已被证明是心血管医学和慢性肾病的一种新型风险标志物，但我们推测，在某些与过量一氧化氮（NO）相关的状态下，如 1-甲基-4-苯基吡啶离子（MPP(+))诱导的神经元损伤，ADMA 可能通过限制高浓度 NO 的毒性作用而具有保护作用。2. 本研究旨在探讨 ADMA 对 MPP(+))诱导的 PC12 细胞凋亡的保护作用及其分子机制。3. 我们发现，外源性应用 ADMA 不仅通过减少线粒体膜电位的丧失，而且通过减弱细胞内活性氧的增加，明显保护 PC12 细胞免受 MPP(+))诱导的细胞毒性和凋亡。此外，ADMA 减弱了 MPP(+))诱导的一氧化氮合酶过度激活和 NO 的过度产生。4. 本研究结果表明，ADMA 引起的保护作用与维持线粒体膜电位有关，并通过抑制一氧化氮合酶活性和限制 NO 的产生来减轻 MPP(+))诱导的细胞内活性氧的产生。
