ERK 参与了 EGF 介导的对乙醛处理的 Caco-2 细胞单层中紧密连接的保护，但不参与黏附连接。
ERK is involved in EGF-mediated protection of tight junctions, but not adherens junctions, in acetaldehyde-treated Caco-2 cell monolayers.
机构信息
Department of Physiology, University of Tennessee Health Science Center, Memphis, 38163, USA.
出版信息
Am J Physiol Gastrointest Liver Physiol. 2011 Jul;301(1):G50-9. doi: 10.1152/ajpgi.00494.2010. Epub 2011 Apr 7.
The role of mitogen-activated protein kinases (MAPK) in the mechanism of EGF-mediated prevention of acetaldehyde-induced tight junction disruption was evaluated in Caco-2 cell monolayers. Pretreatment of cell monolayers with EGF attenuated acetaldehyde-induced decrease in resistance and increase in inulin permeability and redistribution of occludin, zona occludens-1 (ZO-1), E-cadherin, and β-catenin from the intercellular junctions. EGF rapidly increased the levels of phospho-ERK1/2, phospho-p38 MAPK, and phospho-JNK1. Pretreatment of cell monolayers with U-0126 (inhibitor of ERK activation), but not SB-202190 and SP-600125 (p38 MAPK and JNK inhibitors), significantly attenuated EGF-mediated prevention of acetaldehyde-induced changes in resistance, inulin permeability, and redistribution of occludin and ZO-1. U-0126, but not SB-202190 and SP-600125, also attenuated EGF-mediated prevention of acetaldehyde effect on the midregion F-actin ring. However, EGF-mediated preservation of junctional distribution of E-cadherin and β-catenin was unaffected by all three inhibitors. Expression of wild-type or constitutively active MEK1 attenuated acetaldehyde-induced redistribution of occludin and ZO-1, whereas dominant-negative MEK1 prevented EGF-mediated preservation of occludin and ZO-1 in acetaldehyde-treated cells. MEK1 expression did not alter E-cadherin distribution in acetaldehyde-treated cells in the presence or absence of EGF. Furthermore, EGF attenuated acetaldehyde-induced tyrosine-phosphorylation of occludin, ZO-1, claudin-3, and E-cadherin. U-0126, but not SB-202190 and SP-600125, prevented EGF effect on tyrosine-phosphorylation of occludin and ZO-1, but not claudin-3, E-cadherin, or β-catenin. These results indicate that EGF-mediated protection of tight junctions from acetaldehyde requires the activity of ERK1/2, but not p38 MAPK or JNK1/2, and that EGF-mediated protection of adherens junctions is independent of MAPK activities.
在 Caco-2 细胞单层中评估了丝裂原活化蛋白激酶 (MAPK) 在 EGF 介导的预防乙醛诱导的紧密连接破坏机制中的作用。细胞单层的预处理用 EGF 减弱了乙醛诱导的电阻降低和甘露醇通透性增加，以及 occludin、zonula occludens-1 (ZO-1)、E-钙粘蛋白和β-连环蛋白从细胞间连接处的重新分布。EGF 迅速增加磷酸化 ERK1/2、磷酸化 p38 MAPK 和磷酸化 JNK1 的水平。细胞单层的预处理用 U-0126（ERK 激活抑制剂），而不是 SB-202190 和 SP-600125（p38 MAPK 和 JNK 抑制剂），显著减弱了 EGF 介导的预防乙醛诱导的电阻、甘露醇通透性和 occludin 和 ZO-1 重新分布的变化。U-0126 但不是 SB-202190 和 SP-600125，也减弱了 EGF 介导的预防乙醛对中区 F-肌动蛋白环的影响。然而，EGF 介导的 junctio 分布的保留与 E-cadherin 和 β-连环蛋白无关，不受三种抑制剂的影响。野生型或组成型活性 MEK1 的表达减弱了乙醛诱导的 occludin 和 ZO-1 的重新分布，而显性负 MEK1 阻止了 EGF 介导的在乙醛处理细胞中 occludin 和 ZO-1 的保存。MEK1 的表达在存在或不存在 EGF 的情况下均不改变乙醛处理细胞中 E-cadherin 的分布。此外，EGF 减弱了乙醛诱导的 occludin、ZO-1、claudin-3 和 E-cadherin 的酪氨酸磷酸化。U-0126 但不是 SB-202190 和 SP-600125，阻止了 EGF 对 occludin 和 ZO-1 的酪氨酸磷酸化的作用，但对 claudin-3、E-cadherin 或 β-连环蛋白没有作用。这些结果表明，EGF 介导的从乙醛中保护紧密连接需要 ERK1/2 的活性，但不需要 p38 MAPK 或 JNK1/2，并且 EGF 介导的黏附连接的保护独立于 MAPK 活性。
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