Hormesis effect of hydrogen peroxide on the promoter activity of neuropeptide receptor PAC1-R
Hormesis effect of hydrogen peroxide on the promoter activity of neuropeptide receptor PAC1-R
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过氧化氢对神经肽受体PAC1-R启动子活性的兴奋作用
DOI：
10.1111/jfbc.12877
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发表时间：
2019-07-01
影响因子：
4
通讯作者：
Yu, Rongjie
中科院分区：
文献类型：
--
作者：
Huang, Xiaoling;Li, Junfeng;Yu, Rongjie
垂体腺苷酸环化酶激活多肽 (PACAP) 受体 1 (PAC1-R) 是神经肽 PACAP 偏好受体介导的神经保护活性。为了阐明其表达的生物学机制，我们克隆了人ADCYAP1R1基因转录起始位点-2,500至+26的2,526 bp启动子片段，并构建了新型启动子报告系统，命名为pYr-PromDetect-PAC1p。在SH-SY5Y细胞中发现低浓度（10 nM）以剂量依赖性方式抑制PAC1-R的活性。 H2O2对PAC1-R启动子的毒物兴奋效应有助于进一步阐明低剂量活性氧对神经系统的生理效应。实际应用 PAC1-R介导众所周知的神经保护、神经营养和神经发生作用，是神经退行性疾病的重要药物靶点。氧化应激对PAC1-R表达的兴奋效应不仅有助于解释氧化应激对神经系统的兴奋效应，而且为增加PAC1-R的表达用于神经保护或神经生成提供了新的策略。例如，利用低程度的氧化应激来增加 PAC1-R 的表达可能有助于防止随后的手术对神经系统的严重损伤。低浓度H2O2激活PAC1-R启动子有助于进一步阐明低剂量活性氧对神经系统的生理效应。
Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor 1 (PAC1-R) is the neuropeptide PACAP-preferring receptor-mediating neuroprotective activity. In order to clarify the biological mechanism of its expression, we cloned the 2,526 bp promoter fragment from -2,500 to +26 of the transcription initiation site of human ADCYAP1R1 gene and constructed the novel promotor reporter system named pYr-PromDetect-PAC1p. It was found in SH-SY5Y cells low concentration (10 nM) inhibited the activity of PAC1-R in dose-dependent way. The hormesis effect of H2O2 on PAC1-R promoter would help to further clarify the physiological effect of low-dose reactive oxygen on nervous system. Practical applications PAC1-R mediates well-known neuroprotective, neurotrophic, and neurogenesis effects, which is an important drug target for neurodegenerative diseases. The hormesis effects of oxidative stress on PAC1-R expression not only help to explain the hormesis effects of oxidative stress on nerve system, but also offer a novel strategy to increase the expression of PAC1-R for the nerve protection or nerve generation. For example, taking advantage of low degree of oxidative stress to increases the expression of PAC1-R might help prevent subsequent surgical serious injury on the nervous system. The activation of PAC1-R promoter by low concentration of H2O2 would help to further clarify the physiological effect of low-dose reactive oxygen on nervous system.