Disruption of epithelial tight junctions is prevented by cyclic nucleotide-dependent protein kinase inhibitors
Disruption of epithelial tight junctions is prevented by cyclic nucleotide-dependent protein kinase inhibitors
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环核苷酸依赖性蛋白激酶抑制剂可防止上皮紧密连接的破坏
DOI：
10.1007/s004180000143
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发表时间：
2000
影响因子：
2.3
通讯作者：
W. Risau
中科院分区：
文献类型：
--
作者：
Cécile Klingler;U. Kniesel;S. Bamforth;H. Wolburg;B. Engelhardt;W. Risau
抽象。紧密连接（TJ），细胞间连接的最顶端，阻止离子和分子通过细胞旁途径。细胞内信号分子可能参与TJ完整性的调节。为了具体研究蛋白激酶A（PKA）在维持上皮TJ完整性中的作用，进行了钙转换实验，其中在PKA抑制剂H-89或HA-1004不存在或存在的情况下，从EpH 4和MDCK培养基中除去钙。从上皮细胞的培养基中去除钙导致TJ的破坏，其特征在于TJ相关蛋白闭合蛋白ZO-1和ZO-2的膜结合的损失，TJ链的损失，跨上皮电阻的显著降低和对示踪剂的跨上皮渗透性的急剧增加。occludin、ZO-1和ZO-2与肌动蛋白细胞骨架的关联不受影响。相比之下，当在PKA抑制剂H-89或HA-1004存在下进行钙的去除时，所有屏障特征都得到保留。我们的数据表明，从体外上皮细胞培养基中去除钙后，PKA被激活，随后参与TJ的破坏。
Abstract. Tight junctions (TJs), the most apical of the intercellular junctions, prevent the passage of ions and molecules through the paracellular pathway. Intracellular signalling molecules are likely to be involved in the regulation of TJ integrity. In order to specifically investigate the role of protein kinase A (PKA) in the maintenance of epithelial TJ integrity, calcium-switch experiments were performed, in which calcium was removed from EpH4 and MDCK culture medium, in the absence or presence of the PKA inhibitors H-89 or HA-1004. Removal of calcium from the culture media of the epithelial cells resulted in disruption of the TJs, characterised by a loss of membrane association of the TJ-associated proteins occludin, ZO-1 and ZO-2, by a loss of TJ strands, by a marked decrease in the transepithelial electrical resistance and by a dramatic increase in the transepithelial permeability to tracers. The association of occludin, ZO-1 and ZO-2 with the actin cytoskeleton is not affected. In contrast, when the removal of calcium was performed in the presence of either the PKA inhibitor H-89 or HA-1004, all barrier characteristics were preserved. Our data indicate that following the removal of calcium from the culture medium of epithelial cells in vitro, PKA is activated and subsequently is involved in the disruption of TJs.
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影响因子：
4
作者：
C. M. Itallie;James M. Anderson
通讯作者：
C. M. Itallie;James M. Anderson
DOI：
10.1073/pnas.92.13.6072
发表时间：
1995-06
影响因子：
11.1
作者：
R. O. Stuart;S. Nigam
通讯作者：
R. O. Stuart;S. Nigam
DOI：
10.1073/pnas.92.23.10629
发表时间：
1995-11-07
影响因子：
11.1
作者：
NUSRAT, A;GIRY, M;MADARA, JL
通讯作者：
MADARA, JL
人乳腺细胞外钙敏感受体的识别和定位。
DOI：
10.1210/jcem.83.2.4558
发表时间：
1998
期刊：
The Journal of clinical endocrinology and metabolism.
影响因子：
--
作者：
Cheng,I;Klingensmith,ME;Chattopadhyay,N;Kifor,O;Butters,RR;Soybel,DI;Brown,EM
通讯作者：
Brown,EM
AKAP75 中不同束缚和细胞内靶向结构域的表征，AKAP75 是一种将 cAMP 依赖性蛋白激酶 II beta 连接到细胞骨架的蛋白质。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Glantz,SB;Li,Y;Rubin,CS
通讯作者：
Rubin,CS