Academic Journal
Indoxyl Sulfate Upregulates Expression of ICAM-1 and MCP-1 by Oxidative Stress-Induced NF-ĸB Activation
| العنوان: | Indoxyl Sulfate Upregulates Expression of ICAM-1 and MCP-1 by Oxidative Stress-Induced NF-ĸB Activation |
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| المؤلفون: | Tumur, Zohra, Shimizu, Hidehisa, Enomoto, Atsushi, Miyazaki, Hitoshi, Niwa, Toshimitsu |
| المصدر: | American Journal of Nephrology ; volume 31, issue 5, page 435-441 ; ISSN 0250-8095 1421-9670 |
| بيانات النشر: | S. Karger AG |
| سنة النشر: | 2010 |
| الوصف: | Background/Aim: Indoxyl sulfate, a uremic toxin, is considered a risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD). The present study aimed to determine whether indoxyl sulfate increases the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1) by reactive oxygen species (ROS)-induced activation of nuclear factor-ĸB (NF-ĸB) in vascular endothelial cells. Methods: Human umbilical vein endothelial cells (HUVEC) were incubated with indoxyl sulfate. The expression of ICAM-1 and MCP-1 in HUVEC was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Phospho-NF-ĸB p65 (Ser 536), an active form of the NF-ĸB subunit, was determined by Western blotting. Results: Indoxyl sulfate significantly increased the mRNA expression of ICAM-1 and MCP-1 in HUVEC in a time- and concentration-dependent manner. Inhibitors of NF-ĸB (ammonium pyrrolidinedithiocarbamate and isohelenin) and an antioxidant (N-acetyl- L-cysteine) suppressed the indoxyl sulfate-induced expression of ICAM-1 and MCP-1 in HUVEC. Indoxyl sulfate increased phospho- NF-ĸB p65 in HUVEC, and N-acetyl- L-cysteine suppressed it. Conclusions: Indoxyl sulfate upregulates the expression of ICAM-1 and MCP-1 by ROS-induced activation of NF-ĸB in vascular endothelial cells. Thus, indoxyl sulfate may play an important role in the development of CVD in CKD by increasing the endothelial expression of ICAM-1 and MCP-1. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1159/000299798 |
| الاتاحة: | http://dx.doi.org/10.1159/000299798 https://www.karger.com/Article/Pdf/299798 |
| Rights: | https://www.karger.com/Services/SiteLicenses ; https://www.karger.com/Services/SiteLicenses |
| رقم الانضمام: | edsbas.8689D063 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1159/000299798 |
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