Modulation of NO Synthase Gene Expression in CNS Neurons

CNS 神经元中 NO 合酶基因表达的调节

• 批准号: 6789436
• 负责人: ANTHONY PETER YOUNG
• 金额: $ 22.13万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789436
• 关键词: Retroviridae; biological signal transduction; central nervous system; fusion gene; gene expression; genetic promoter element; genetic regulatory element; genetically modified animals; ischemia; laboratory mouse; methamphetamine; nerve injury; neurochemistry; neurogenetics; nitric oxide synthase; peripheral nervous system

DESCRIPTION (provided by applicant): The long term objective of this application is to elucidate the molecular mechanisms by which nitric oxide synthase I (NOS1) gene expression is modulated in the central and peripheral nervous systems in response to methamphetamine-induced, ischemic, and traumatic injury, respectively. Specifically, we hope to identify and characterize cis elements that regulate transcription of the human NOS1 gene, and to identify factors and signal transduction pathways that act vis a vis these elements to induce NOS1 in response to these types of injuries. NOS1 is a complex gene with at least three distinct promoter complexes regulating transcription in the CNS. Specific aim 1 proposes to identify cis elements that are important for CNS-specific expression of the NOS1 promoters. These studies utilize retroviruses that express an EGFP reporter under transcriptional control by individual human NOS1 promoters and cell culture as well as in vivo assay systems. Specific aim 2 proposes to determine whether individual human NOS1 promoters are activated in response to methamphetamine treatment, ischemia, and peripheral nerve injury, respectively. In these studies, lines of transgenic mice expressing different NOS1-lac Z fusion genes will be subjected to the each of the three neuronal injury models, followed by analysis of fusion gene expression. Specific aim 3 proposes to determine whether these fusion genes are activated in cortical neuronal cultures by treatments producing excitotoxicity and by modulation of signaling pathways. Expression of nitric oxide (NO) is correlated with neuroprotection in neurodegenerative disease and, depending on cellular context, NO also acts as a potent neurotoxin. Indeed, NO toxicity is a major cause of neuronal cell death during stroke. Consequently, it is critical to understand all processes that contribute to the formation of NOS in the CNS. By focusing on transcriptional control of human NOS 1, this application has great potentia1 significance in the context of new drug discovery and in providing a more profound understanding of the plasticity of gene expression in the CNS.

描述（由申请人提供）：该项目的长期目标

项目成果

A promoter element with enhancer properties, and the orphan nuclear receptor RORalpha, are required for Purkinje cell-specific expression of a Gi/o modulator.

浦肯野细胞特异性表达 Gi/o 调节剂需要具有增强子特性的启动子元件和孤儿核受体 RORalpha。

• DOI: 10.1016/j.mcn.2006.11.013
• 发表时间: 2007
• 期刊: Molecular and cellular neurosciences
• 作者: Serinagaoglu,Yelda;Zhang,Rui;Zhang,Yufang;Zhang,Linda;Hartt,Greg;Young,AnthonyP;Oberdick,John
• 通讯作者: Oberdick,John

The 5'2 promoter of the neuronal nitric oxide synthase dual promoter complex mediates inducibility by nerve growth factor.

神经元一氧化氮合酶双启动子复合物的 52 启动子介导神经生长因子的诱导性。

• DOI: 10.1016/s0169-328x(99)00293-4
• 发表时间: 2000
• 期刊: Brain research. Molecular brain research
• 作者: Rife,TK;Xie,J;Redman,C;Young,AP
• 通讯作者: Young,AP