CYCLIC GMP PHOSPHODIESTERASES IN PC12 DIFFERENTIATION

PC12 分化中的环状 GMP 磷酸二酯酶

• 批准号: 6351837
• 负责人: JOHN Kelley BENTLEY
• 金额: $ 10.68万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-10 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6351837
• 关键词: 3'5' cyclic nucleotide phosphodiesterase; PC12 cells; animal genetic material tag; cell differentiation; complementary DNA; cyclic GMP; developmental neurobiology; enzyme activity; immunocytochemistry; laboratory rat; messenger RNA; molecular cloning; neurogenesis; neurons; nucleic acid sequence; sympathetic ganglion

DESCRIPTION NGF causes a rapid loss of cGMP-stimulated cyclic nucleotide phosphodiesterase (PDE2) activity in PC12 cells (50% reduction after 24 hours). Longer treatment with NGF results in a greater than 80% reduction in PDE 2 activity. PDE2 mRNA is not rapidly decreased but CaM-stimulated PDE (PDE1) mRNAs are induced by NGF-differentiation. NGF action to promote neuronal survival or PC12 differentiation is hypothesized to have effects on transcription levels and on post - translational modification of distinct PDEs, and proteins regulating them, to decrease the overall PDE activity of the cell. Sympathetic differentiation is further hypothesized to shift cyclic nucleotide metabolism from a cyclic GMP-regulated to a calcium-regulated state. The specific aims of the study are 1) structural characterization of PDE1 and PDE2 cDNAs from PC12 and sympathetic neurons 2) assessment of NGF effects on PC12 and rat sympathetic ganglia PDE mRNAs and proteins and 3) identification of PDE1- and PDE2-interacting proteins through molecular cloning and immunochemical analysis.

描述NGF导致CGMP刺激的环状核苷酸的迅速丧失 PC12细胞中的磷酸二酯酶（PDE2）活性（24后降低了50％ 小时）。 使用NGF治疗的较长的治疗导致降低超过80％ 在PDE 2活动中。 PDE2 mRNA不会迅速减少，但cam刺激 PDE（PDE1）mRNA是通过NGF分化诱导的。 NGF行动促进 假设神经元存活或PC12分化对 转录水平和邮政 - 转化的不同 PDE和调节它们的蛋白质，以降低 细胞。 进一步假设同情分化以移动 从环状GMP调节到A的环状核苷酸代谢 钙调节状态。 该研究的具体目的是1）PDE1的结构表征 PC12和交感神经元的PDE2 cDNA 2）NGF评估 对PC12和大鼠交感神经节PDE mRNA和蛋白质的影响以及3） 通过分子鉴定PDE1和PDE2相互作用蛋白 克隆和免疫化学分析。