Mildly oxidized low density lipoprotein induces contraction of human endothelial cells through activation of Rho/Rho kinase and inhibition of myosin light chain phosphatase
Mildly oxidized low density lipoprotein induces contraction of human endothelial cells through activation of Rho/Rho kinase and inhibition of myosin light chain phosphatase
复制标题
DOI：
10.1074/jbc.274.43.30361
复制
发表时间：
1999-10-22
影响因子：
4.8
通讯作者：
Siess, W
中科院分区：
文献类型：
--
作者：
Essler, M;Retzer, M;Siess, W
轻度氧化的低密度脂蛋白（MOX-LDL）与内皮的早期动脉粥样硬化反应至关重要，并通过未知的信号途径增加内皮通透性。在这里，我们表明（i）将汇合的人内皮细胞（HUVEC）暴露于MOX-LDL，但对天然LDL的暴露不会在几分钟内诱导肌动蛋白应激纤维和细胞间间隙的形成，从而导致内皮通透性的增加； （ii）MOX-LDL诱导肌球蛋白轻链（MLC）磷酸酶的短暂降低，该磷酸酶与MLC磷酸化的增加相似； （iii）MOX-LDL刺激的磷酸化MLC掺入应力纤维中； （iv）C3转移酶从肉毒杆菌（一种特定的Rho抑制剂）和Rho激酶的抑制剂Y-27632抑制了细胞骨架重排和MLC磷酸化； （v）MOX-LDL不会增加细胞内Ca2+浓度。我们的数据表明，MOX-LDL通过激活RHO及其效应子Rho激酶诱导内皮细胞收缩，从而抑制MLC磷酸酶并磷酸化MLC。我们建议抑制这种新型MOX-LDL的细胞信号传导途径可能与预防动脉粥样硬化有关。
Mildly oxidized low density lipoprotein (mox-LDL) is critically involved in the early atherogenic responses of the endothelium and increases endothelial permeability through an unknown signal pathway. Here we show that (i) exposure of confluent human endothelial cells (HUVEC) to mox-LDL but not to native LDL induces the formation of actin stress fibers and intercellular gaps within minutes, leading to an increase in endothelial permeability; (ii) mox-LDL induces a transient decrease in myosin light chain (MLC) phosphatase that is paralleled by an increase in MLC phosphorylation; (iii) phosphorylated MLC stimulated by mox-LDL is incorporated into stress fibers; (iv) cytoskeletal rearrangements and MLC phosphorylation are inhibited by C3 transferase from Clostridium botulinum, a specific Rho inhibitor, and Y-27632, an inhibitor of Rho kinase; and (v) mox-LDL does not increase intracellular Ca2+ concentration. Our data indicate that mox-LDL induces endothelial cell contraction through activation of Rho and its effector Rho kinase which inhibits MLC phosphatase and phosphorylates MLC. We suggest that inhibition of this novel cell signaling pathway of mox-LDL could be relevant for the prevention of atherosclerosis.