Zwijsen R M, de Haan L H, Oosting J S, Pekelharing H L, Koeman J H
Department of Toxicology, Agricultural University, Wageningen, The Netherlands.
Atherosclerosis. 1990 Nov;85(1):71-80. doi: 10.1016/0021-9150(90)90184-k.
Inhibition by tumor promoting chemicals of intercellular communication via gap junctions may be important in carcinogenesis. In order to investigate the possible role of gap junctional intercellular communication in atherogenesis, we examined the effect of known inhibitors of intercellular communication, 12-O-tetradecanoylphorbol-13-acetate (TPA) and cigarette smoke condensate (CSC), and low density lipoproteins (LDL) and high density lipoproteins (HDL) on cellular communication in smooth muscle cells of human and rat by the microinjection-dye transfer technique. When lucifer yellow CH solution is injected into a cell, the average numbers of human and rat smooth muscle cells that become fluorescent is about 22 and 6, respectively. The tumor promoter (TPA) almost completely blocked gapjunctional communication between smooth muscle cells at 100 ng/ml after 4 h exposure. LDL and CSC were able to inhibit intercellular communication in human and rat cells in a dose-dependent manner up to 60%. LDL-pretreatment of human smooth muscle cells did not affect inhibition of intercellular communication, which suggests that this effect is mainly non-receptor mediated. HDL did not influence junctional communication. The results indicate that inhibition of intercellular communication may also contribute to the pathogenesis of atherosclerotic lesions, such as plaques.
肿瘤促进化学物质通过间隙连接抑制细胞间通讯可能在致癌过程中起重要作用。为了研究间隙连接细胞间通讯在动脉粥样硬化发生中的可能作用，我们通过显微注射-染料转移技术，检测了已知的细胞间通讯抑制剂十四烷酰佛波醇乙酯（TPA）、香烟烟雾冷凝物（CSC）以及低密度脂蛋白（LDL）和高密度脂蛋白（HDL）对人和大鼠平滑肌细胞间通讯的影响。当将荧光素黄CH溶液注入一个细胞时，分别约有22个和6个人和大鼠平滑肌细胞会发出荧光。在暴露4小时后，肿瘤促进剂（TPA）在100 ng/ml时几乎完全阻断了平滑肌细胞间的间隙连接通讯。LDL和CSC能够以剂量依赖的方式抑制人和大鼠细胞间的通讯，抑制率高达60%。对人平滑肌细胞进行LDL预处理并不影响细胞间通讯的抑制，这表明这种效应主要是非受体介导的。HDL不影响连接通讯。结果表明，细胞间通讯的抑制也可能有助于动脉粥样硬化病变（如斑块）的发病机制。
