- 期刊
The Arrhythmogenic Effect of Protein-Bound Uremic Toxin p-Cresylsulfate: An In Vitro Study
摘要
Background: p-Cresylsulfate (PCS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease. Previous studies have indicated that serum total PCS levels are significantly increased in the presence of abnormal corrected QT (QTc) intervals, and that they are associated with QTc prolongation. However, the QTc prolongation effect of PCS remains unclear. The current study aimed to investigate the arrhythmogenic effect of PCS using in vitro experiments and computer simulation. Methods: The arrhythmogenic effect of PCS was evaluated by incubating H9c2 rat ventricular cardiomyocytes in vitro with increasing concentrations of PCS. Electrophysiological studies and mathematical computer simulations were performed. Results: In vitro, the delayed rectifier potassium current (I_K) was significantly decreased in a dose-dependent manner after treatment with PCS. The modulation of PCS on I_K was through regulation of the phosphorylation of the major potassium ion channel protein Kv2.1. In computer simulations, the decrease in I_K induced by PCS prolonged the action potential duration (APD) and sped up the re-entrant wave, which is known to be a trigger mechanism for lethal ventricular arrhythmias. Conclusions: PCS significantly downregulated the phosphorylation of the I_K channel protein Kv2.1 and I_K current activity, which increased the cardiomyocyte APD. This was observed both in vitro and in the computer O'Hara-Rudy dynamic human ventricular model. These findings suggest that PCS may play a key role in the development of cardiac arrhythmias.
延伸閱讀
- 陳詩珊（2013）。Arsenic, Gene Polymorphism of Insulin-related Enzymes and enal Cell Carcinoma〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-2607201316281000
- 李志宏（2003）。Effects and Interactions of Low Doses of UVB and Arsenic on Keratinocyte Apoptosis〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0011-0707200815595541
- Sun, Y., & Shang, D. (2015). Inhibitory Effects of Antimicrobial Peptides on Lipopolysaccharide-Induced Inflammation. Mediators of Inflammation, 2015(), 457-464-041. https://doi.org/10.1155/2015/167572
- 洪蓴仁（2008）。Characterization of the relationship between mouse uterine24p3 protein and cytokines〔碩士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2008.10638
- Shen, C. Y., Wu, P. C., Li, K. J., Wu, C. H., Hsieh, S. C., & Yu, C. L. (2011). The Clinical Significance of Anti-β2-glycoprotein I Antibody in Antiphospholipid Syndrome. Formosan Journal of Rheumatology, 25(1&2), 56-60. https://doi.org/10.6313/FJR.2011.25(1-2).09