GAP JUNCTIONS IN VASCULAR SMOOTH MUSCLE--GROWTH CONTROL

描述：伯特博士，GAP文献的长期撰稿人 结点门控和调节，提出了详细的分析 缝隙连接偶联对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，与一般的教义背道而驰 在细胞增殖过程中，细胞间的偶联作用减弱。 相反，她发现，将扩散和增长停滞不前进行比较 A7r5细胞，通过染料扩散测量的偶联程度降低，但电 耦合性增强。这一变化与 单通道电导分布(增加150ps通道和 70ps通道的减少)以及两者的RNA水平的相反变化 在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，但会抑制 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，在没有证据的情况下，阴离子偏好将有利于 相关信使系统)。归根结底，该提案是针对 确定缝隙连接在相关的增殖反应中的作用 动脉粥样硬化。为此，PI部分地描述了 三种细胞系统--A7r5细胞、原代平滑肌细胞(SMCs)和 转基因HeLa细胞--血清剥夺生长条件的建立 抑制PDGF和OX-LDL的促有丝分裂作用。

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.