https://scholars.lib.ntu.edu.tw/handle/123456789/578487
標題: | Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism | 作者: | Peng Y.-S. Lin Y.-T. Chen Y. KUAN-YU HUNG Wang S.-M. |
關鍵字: | Adherens Junction; Endothelial Cells; Free Radicals; Indoxyl Sulfate; Stress Fiber | 公開日期: | 2012 | 卷: | 113 | 期: | 3 | 起(迄)頁: | 1034-1043 | 來源出版物: | Journal of Cellular Biochemistry | 摘要: | Uremic patients have a much higher risk of cardiovascular diseases and death. Uremic toxins are probably involved in the development of vascular endothelial dysfunction. Indoxyl sulfate (IS) is a uremic toxin that accumulates with deterioration of renal function. This study explored the effects of IS on the adherens junctions of vascular endothelial cells and revealed the underlying mechanism. Bovine pulmonary artery endothelial cells (BPAECs) were treated with IS, and the distribution of vascular endothelial cadherin (VE-cadherin), p120-catenin, b-catenin, and stress fibers was examined by immunofluorescence. IS treatment resulted in disruption of intercellular contacts between BPAECs with prominent parallel-oriented intracellular stress fiber formation. Intracellular free radical levels which measured by flow cytometry increased after IS treatment. The antioxidant, MnTMPyP, and an ERK pathway inhibitor, U0126, both significantly prevented ISinduced disruption of intercellular contacts. Western blotting analyses demonstrated that IS-induced phosphorylation of myosin light chain kinase (MLCK) and myosin light chains (MLC) as well as activation of extracellular-signal-regulated protein kinase (ERK1/ERK2). Pretreatment with MnTMPyP prevented ERK1/2 phosphorylation. U0126 prevented the IS-induced MLCK and MLC phosphorylation. MEK-ERK acted as the upstream regulator of the MLCK-MLC pathway. These findings suggest that the superoxide anion-MEK-ERK-MLCKMLC signaling mediates IS-induced junctional dispersal of BPAECs. ? 2011 Wiley Periodicals, Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84863288392&doi=10.1002%2fjcb.23435&partnerID=40&md5=f2311059538ee167fb53a7b140948a0f https://scholars.lib.ntu.edu.tw/handle/123456789/578487 |
ISSN: | 0730-2312 | DOI: | 10.1002/jcb.23435 | SDG/關鍵字: | antioxidant; antioxidant MnTMPyp; beta catenin; catenin; free radical; indican; mitogen activated protein kinase 1; mitogen activated protein kinase 3; myosin light chain; myosin light chain kinase; protein p120; superoxide; unclassified drug; uo 126; vascular endothelial cadherin; animal cell; article; cell communication; cell junction; cell viability; controlled study; cytoskeleton; endothelium cell; enzyme activation; flow cytometry; immunofluorescence; microvascular endothelial cell; nonhuman; priority journal; protein phosphorylation; signal transduction; stress fiber; vascular endothelial cell; Western blotting; Adherens Junctions; Animals; Butadienes; Cell Survival; Cells, Cultured; Cytoskeleton; Endothelial Cells; Endothelium, Vascular; Extracellular Signal-Regulated MAP Kinases; Indican; MAP Kinase Signaling System; Myosin Light Chains; Myosin-Light-Chain Kinase; Nitriles; Superoxides; Bovinae |
顯示於: | 醫學系 |
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