The volatile anesthetic isoflurane increases endothelial adenosine generation via microparticle ecto-5'-nucleotidase (CD73) release.
The volatile anesthetic isoflurane increases endothelial adenosine generation via microparticle ecto-5'-nucleotidase (CD73) release.
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DOI：
10.1371/journal.pone.0099950
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lee HT
中科院分区：
文献类型：
--
作者：
Kim M;Ham A;Kim KY;Brown KM;Lee HT
血管内皮细胞功能障碍在急、慢性器官损伤中十分常见。异氟醚是围手术期广泛使用的一种卤代挥发性麻醉剂，可预防内皮细胞死亡和炎症。在这项研究中，我们测试了异氟醚是否诱导内皮细胞胞外-5‘-核苷酸酶(CD73)和细胞保护性腺苷的产生来保护内皮细胞免受损伤。临床相关浓度的异氟醚诱导培养的人脐静脉或小鼠肾小球内皮细胞CD73活性和腺苷生成增加。令人惊讶的是，异氟醚介导的内皮CD73活性的诱导在1小时内发生，并且没有合成新的CD73。我们发现异氟醚能迅速增加含有内皮微粒的CD73进入细胞培养上清液。事实上，从异氟醚处理的内皮细胞中分离出的微粒具有显著更高的CD73活性以及增加的CD73蛋白。在体内，与戊巴比妥钠麻醉小鼠的血浆相比，异氟醚麻醉小鼠的血浆中内皮细胞来源的CD144+CD73+微粒显著增加，并且微粒CD73活性增加。CD73选择性抑制剂(APCP)支持CD73在异氟烷介导的内皮保护中的关键作用，可阻止异氟烷诱导的人内皮细胞炎症和凋亡保护。此外，异氟醚通过肌球蛋白磷酸酶靶向亚单位-1和肌球蛋白轻链磷酸化激活内皮细胞Rho激酶。此外，选择性Rho激酶抑制剂(Y27632)显著减弱了异氟烷诱导的含有CD73微粒的释放。综上所述，我们得出结论，挥发性麻醉剂异氟醚导致Rho激酶介导的含有预形成CD73的内皮微粒的释放，并增加腺苷的产生，以保护内皮细胞凋亡和炎症。
Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether isoflurane induces endothelial ecto-5′-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, isoflurane-induced release of CD73 containing microparticles was significantly attenuated by a selective Rho kinase inhibitor (Y27632). Taken together, we conclude that the volatile anesthetic isoflurane causes Rho kinase-mediated release of endothelial microparticles containing preformed CD73 and increase adenosine generation to protect against endothelial apoptosis and inflammation.
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影响因子：
3.5
作者：
Colgan, Sean P;Eltzschig, Holger K;Eckle, Tobias;Thompson, Linda F
通讯作者：
Thompson, Linda F
DOI：
10.1152/ajprenal.00290.2007
发表时间：
2007-12-01
影响因子：
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作者：
Kim, Minjae;Kim, Mihwa;Lee, H. Thomas
通讯作者：
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DOI：
10.4049/jimmunol.1003379
发表时间：
2011-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Haskó G;Csóka B;Koscsó B;Chandra R;Pacher P;Thompson LF;Deitch EA;Spolarics Z;Virág L;Gergely P;Rolandelli RH;Németh ZH
通讯作者：
Németh ZH
影响因子：
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作者：
Fuentes, JM;Talamini, MA;De Maio, A
通讯作者：
De Maio, A
DOI：
10.1161/atvbaha.110.218123
发表时间：
2011-01-01
影响因子：
8.7
作者：
Dignat-George, Francoise;Boulanger, Chantal M.
通讯作者：
Boulanger, Chantal M.