Physiological Concentration of H2O2 Supports Dopamine Neuronal Survival via Activation of Nrf2 Signaling in Glial Cells
Physiological Concentration of H2O2 Supports Dopamine Neuronal Survival via Activation of Nrf2 Signaling in Glial Cells
复制标题
H2O2 的生理浓度通过激活神经胶质细胞中的 Nrf2 信号传导来支持多巴胺神经元存活
DOI：
10.1007/s10571-020-00844-z
复制
发表时间：
2020-04
影响因子：
4
通讯作者：
Feng Zhang
中科院分区：
文献类型：
--
作者：
Guoqing Wang;Qiuyu Yang;Changqing Zheng;Daidi Li;Jingjie Li;Feng Zhang
传统上，过氧化氢（H2 O2）是由细胞氧化代谢形成的，通常被视为有毒废物。事实上，H2 O2是神经元-胶质细胞信号传导和突触传递的有益信使。因此，H2 O2是一把双刃剑，H2 O2产生的神经保护与神经毒性难以定义。核因子红细胞2相关因子2（Nrf 2）已被认为是神经元生长的细胞内调节因子。Nrf 2的失活参与了帕金森病（PD）的发生发展。因此，适当激活Nrf 2对PD的预防和治疗至关重要。本研究的目的是探讨是否过氧化氢赋予神经保护作用，以支持神经元的存活。将H2 O2以浓度和时间依赖性方式加入原代神经元-胶质细胞、神经元-星形胶质细胞和神经元-小胶质细胞共培养物中。H2 O2增加多巴胺（DA）神经元的存活浓度和时间依赖性的方式。此外，神经胶质细胞Nrf 2激活参与H2 O2支持的DA神经元的存活与以下现象。首先，H2 O2激活Nrf 2信号通路。其次，过氧化氢产生有益的神经保护神经元胶质细胞，神经元星形胶质细胞和神经元小胶质细胞共培养，但不是在神经元富集的文化。第三，沉默神经胶质细胞中的Nrf 2废除H2 O2赋予DA神经元的生存。这项研究表明，生理浓度的过氧化氢支持DA神经元的存活通过激活神经胶质细胞中的Nrf 2信号。我们的数据允许重新评估过氧化氢在PD发病机制和治疗策略中的作用。
Traditionally, hydrogen peroxide (H2O2) was formed from cellular oxidative metabolism and often viewed as toxic waste. In fact, H2O2 was a benefit messenger for neuron-glia signaling and synaptic transmission. Thus, H2O2 was a double-edged sword and neuroprotection vs. neurotoxicity produced by H2O2 was difficult to define. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been implicated as an intracellular regulator of neuronal growth. Inactivation of Nrf2 participated in the development of Parkinson's disease (PD). Thus, suitable activation of Nrf2 was essential for the prevention and treatment of PD. This study aimed to explore whether H2O2-conferred neuroprotective effects to support neuronal survival. H2O2 were added into primary neuron-glia, neuron-astroglia and neuron-microglia co-cultures in concentration- and time-dependent manners. H2O2 increased dopamine (DA) neuronal survival in concentration- and time-dependent manners. In addition, glial cells Nrf2 activation involved in H2O2-supported DA neuronal survival with the following phenomenons. First, H2O2 activated Nrf2 signaling pathway. Second, H2O2 generated beneficial neuroprotection in neuron-glia, neuron-astroglia and neuron-microglia co-cultures but not in neuron-enriched cultures. Third, silence of Nrf2 in glial cells abolished H2O2-conferred DA neuronal survival. This study demonstrated that physiological concentration of H2O2-supported DA neuronal survival via activation of Nrf2 signaling in glial cells. Our data permit to re-evaluate the role of H2O2 in the pathogenesis and therapeutic strategies for PD.
登录
查看更多内容
影响因子：
9.3
作者：
Liddell JR;Lehtonen S;Duncan C;Keksa-Goldsteine V;Levonen AL;Goldsteins G;Malm T;White AR;Koistinaho J;Kanninen KM
通讯作者：
Kanninen KM
DOI：
10.1016/j.bbadis.2014.03.003
发表时间：
2014-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
C. P. Fonseca;Susana Gama;Ana Saavedra;G. Baltazar
通讯作者：
C. P. Fonseca;Susana Gama;Ana Saavedra;G. Baltazar
DOI：
10.1523/jneurosci.23-01-00269.2003
发表时间：
2003-01
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
A. Kamsler;M. Segal
通讯作者：
A. Kamsler;M. Segal
影响因子：
9.3
作者：
Zhang, Bei;Wang, Guoqing;Zhang, Feng
通讯作者：
Zhang, Feng
影响因子：
4.7
作者：
P. Naveilhan;I. Neveu;F. Jehan;C. Baudet;D. Wion;P. Brachet
通讯作者：
P. Naveilhan;I. Neveu;F. Jehan;C. Baudet;D. Wion;P. Brachet