Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 조인호 | * |
dc.contributor.author | 서정원 | * |
dc.contributor.author | 박정현 | * |
dc.contributor.author | 이현주 | * |
dc.contributor.author | 이지영 | * |
dc.date.accessioned | 2016-08-27T04:08:33Z | - |
dc.date.available | 2016-08-27T04:08:33Z | - |
dc.date.issued | 2016 | * |
dc.identifier.issn | 0891-5849 | * |
dc.identifier.issn | 1873-4596 | * |
dc.identifier.other | OAK-16024 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/217834 | - |
dc.description.abstract | We reported that arsenite causes an acute decrease in nitric oxide (NO) production by increasing phosphorylation of endothelial NO synthase at threonine 497 (eNOS-Thr(497)); however, the detailed mechanism has not yet been clarified. Here, we investigated the kinase involving in arsenite-stimulated eNOS-Thr(497) phosphorylation. Although treatment with H-89, a known protein kinase A (PKA) inhibitor, inhibited arsenite-stimulated eNOS-Thr(497) phosphorylation, no inhibition was found in cells treated with other PKA inhibitors, including Rp-8-Br-cAMPS or PKI. Based on previous reports, we also tested whether RhoA mediates arsenite-stimulated eNOS-Thr(497) phosphorylation and found that arsenite causes an acute increase in RhoA activity. Ectopic expression of dominant negative (DN)-RhoA significantly reversed arsenite-stimulated eNOS-Thr(497) phosphorylation. An in vitro phosphorylation assay also revealed that the well-known Rho effectors, Rho-associated protein kinase 1 /2 (ROCK1 /2), directly phosphorylate eNOS-Thr(497). Y27632, a selective ROCK inhibitor, reversed arsenite-stimulated eNOS-Thr(497) phosphorylation. However, overexpression of a small interfering RNA (siRNA) against ROCK1 /2 or DN-ROCK did not reverse arsenite-stimulated eNOS-Thr(497) phosphorylation, thereby providing no conclusive evidence of a role for ROCK1 /2. Knockdown of PKC-related protein kinase 1 /2, another Rho effector, also did not reverse arsenite-stimulated eNOS-Thr(497) phosphorylation. In contrast, we found that transfection with an siRNA against citron Rho-interacting kinase (CRIK), the other downstream effector of Rho, significantly reversed the arsenite-induced eNOS-Thr(497) phosphorylation that was accompanied by restoration of eNOS enzymatic activity repressed by arsenite. Moreover, CRIK directly phosphorylated eNOS-Thr(497) in vitro. Finally, we also found that arsenite increased eNOS-Thr(497) phosphorylation and decreased acetylcholine-induced vessel relaxation in rat aortas. In conclusion, we demonstrate that arsenite acutely inhibits eNOS enzymatic activity and vessel relaxation in part by increasing the RhoA/CRIK/eNOS-Thr(497) phosphorylation signaling axis, which provides a molecular mechanism underlying arsenite-induced impaired vascular diseases. (C) 2015 Elsevier Inc. All rights reserved. | * |
dc.language | English | * |
dc.publisher | ELSEVIER SCIENCE INC | * |
dc.subject | Arsenite | * |
dc.subject | Vascular disease | * |
dc.subject | Nitric oxide | * |
dc.subject | Endothelial nitric oxide synthase | * |
dc.subject | Phosphorylation | * |
dc.subject | Rho | * |
dc.subject | Citron Rho-interacting kinase | * |
dc.subject | Ex vivo vessel relaxation | * |
dc.title | Citron Rho-interacting kinase mediates arsenite-induced decrease in endothelial nitric oxide synthase activity by increasing phosphorylation at threonine 497: Mechanism underlying arsenite-induced vascular dysfunction | * |
dc.type | Article | * |
dc.relation.volume | 90 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 133 | * |
dc.relation.lastpage | 144 | * |
dc.relation.journaltitle | FREE RADICAL BIOLOGY AND MEDICINE | * |
dc.identifier.doi | 10.1016/j.freeradbiomed.2015.11.020 | * |
dc.identifier.wosid | WOS:000367396600013 | * |
dc.identifier.scopusid | 2-s2.0-84948461563 | * |
dc.author.google | Seo, Jungwon | * |
dc.author.google | Cho, Du-Hyong | * |
dc.author.google | Lee, Hyeon-Ju | * |
dc.author.google | Sung, Min-Sun | * |
dc.author.google | Lee, Jee Young | * |
dc.author.google | Won, Kyung-Jong | * |
dc.author.google | Park, Jung-Hyun | * |
dc.author.google | Jo, Inho | * |
dc.contributor.scopusid | 조인호(26643129000;56663841900) | * |
dc.contributor.scopusid | 이현주(57204537944) | * |
dc.contributor.scopusid | 이지영(55540732300;57212925259) | * |
dc.date.modifydate | 20240222162940 | * |