Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachky ave., Rostov-on-Don 344090, Russia.
Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachky ave., Rostov-on-Don 344090, Russia.
J Photochem Photobiol B. 2019 Oct;199:111603. doi: 10.1016/j.jphotobiol.2019.111603. Epub 2019 Aug 22.
Photodynamic therapy (PDT) is used for killing of malignant cells in tumors including brain cancer. It can also damage normal neurons and glial cells. Nitric oxide (NO) is known to control PDT-induced cell death. To study the mechanisms that regulate NO generation in photosensitized neurons and glial cells, we used a simple model object - isolated crayfish mechanoreceptor that consists of a single sensory neuron surrounded by glial cells. PDT induced NO generation in glial cells, neuronal dendrites, and, less, in soma and axon. Using modulators of the cytosolic Ca level and nuclear factor-kappa B (NF-κB) activity, we showed that Ca and NF-κB regulate NO generation in the photosensitized neurons and glia. Actually, NO production was stimulated by 4-fold cadmium chloride (CdCl) concentration in the saline, Ca ionophore ionomycine, or inhibition of Ca-ATPase in the endoplasmic reticulum by 2,5-ditert-butylbenzene-1,4-diol (tBuBHQ). Oppositely, CdCl or nifedipine, blockers of Ca channels in the plasma membrane, decreased NO generation. NO production was also inhibited by S-methylthiouronium sulfate (SMT), inhibitor of Ca-independent inducible NO synthase. SMT also prevented the stimulation of PDT-induced NO generation by NF-κB activator prostratin. This suggests the involvement of both Ca-dependent neuronal NO synthase and Ca-independent inducible NO synthase, which is regulated by NF-κB, in NO production in the crayfish neurons and glia.
光动力疗法（PDT）用于杀死肿瘤中的恶性细胞，包括脑癌。它还会损伤正常神经元和神经胶质细胞。一氧化氮（NO）已知可控制 PDT 诱导的细胞死亡。为了研究调节光敏神经元和神经胶质细胞中 NO 生成的机制，我们使用了一个简单的模型对象 - 分离的螯虾机械感受器，它由一个被神经胶质细胞包围的单个感觉神经元组成。PDT 诱导神经胶质细胞、神经元树突以及较少的胞体和轴突中产生 NO。使用细胞溶质 Ca 水平和核因子-kappa B（NF-κB）活性的调节剂，我们表明 Ca 和 NF-κB 调节光敏神经元和神经胶质中的 NO 生成。实际上，氯化镉（CdCl）在盐水中的浓度增加 4 倍、钙离子载体离子霉素或内质网 Ca-ATP 酶的抑制剂 2,5-二叔丁基对苯二酚（tBuBHQ）可刺激 NO 产生。相反，CdCl 或硝苯地平（钙通道在质膜中的阻滞剂）降低了 NO 的生成。S-甲基硫代硫酸铵（SMT），钙非依赖性诱导型一氧化氮合酶的抑制剂，也抑制了 NO 的产生。SMT 还阻止了 NF-κB 激活剂 prostratin 对 PDT 诱导的 NO 生成的刺激。这表明 Ca 依赖性神经元型一氧化氮合酶和 Ca 非依赖性诱导型一氧化氮合酶都参与了螯虾神经元和神经胶质中的 NO 生成，后者受 NF-κB 调节。
