GAP JUNCTIONS IN VASCULAR SMOOTH MUSCLE--GROWTH CONTROL

血管平滑肌的间隙连接——生长控制

• 批准号: 6030845
• 负责人: JANIS M BURT
• 金额: $ 20.91万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-15 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6030845
• 关键词: atherosclerosis; cell growth regulation; gap junctions; human tissue; membrane channels; membrane potentials; pathologic process; tissue /cell culture; vascular smooth muscle

DESCRIPTION: Dr. Burt, a long contributor to the literature on gap junctional gating and regulation, proposes a detailed analysis of the response of gap junctional coupling to mitogenic stimuli (both acute and chronic) in three different cell lines. The basis of these investigations is an exciting finding by the PI that runs contrary to the general dogma that intercellular coupling is decreased during cellular proliferation. Instead, she has found that, comparing proliferating and growth arrested A7r5 cells, coupling as measured by dye spread decreases, but electrical coupling increases. This change is coincident with a change in the distribution of single channel conductances (increase in 150pS channel and decrease in 70pS channel) and inverse changes in the RNA levels of the two major connexins expressed in these cells (i.e. increase in Cx40 and decrease in 43). The hypothesis that arises from these data is that the proliferative state may need to retain electrical coupling, but depresses the exchange of larger metabolites and messengers, and achieves this through differential expression of connexins with varying permselectivities (it is assumed, without substantiation, that anionic preference would favor the relevant messenger system). Ultimately the proposal is directed towards defining a role for gap junctions in the proliferative responses associated with Atherosclerosis. Towards this end, the PI has partially characterized three cell systems--A7r5 cells, primary Smooth Muscle Cells (SMCs), and transfected HeLa cells--and established conditions for serum deprived growth arrest and PDGF and ox-LDL mitogenic stimulation.

描述：伯特博士，长期致力于差距的文献 连接门控和调节，提出了详细的分析， 缝隙连接偶联对促有丝分裂刺激的反应（急性和 慢性）在三种不同的细胞系中。 这些调查的基础 是PI的一个令人兴奋的发现， 在细胞增殖过程中细胞间偶联减少。 相反，她发现， A7 r5细胞，如通过染料扩散测量的偶联降低，但电偶联降低。 耦合增加。 这一变化与 单沟道电导的分布（在150 pS沟道中增加， 70 pS通道的减少）和两种细胞的RNA水平的反向变化。 这些细胞中表达的主要连接蛋白（即Cx40增加和减少 43）。 从这些数据中得出的假设是， 增殖状态可能需要保持电耦合，但抑制 更大的代谢物和信使的交换，并通过 具有不同渗透选择性的连接蛋白的差异表达（它是 假设，没有证实，阴离子偏好将有利于 相关信使系统）。 最终，该提案旨在 明确间隙连接在与细胞增殖相关的增殖反应中的作用 关于Atheroids 为此，PI部分描述了 三种细胞系统--A7 r5细胞、原代平滑肌细胞（SMC）和 转染的HeLa细胞-并建立了血清剥夺生长的条件 抑制和PDGF和ox-LDL促有丝分裂刺激。