Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science.
Department of Pharmacology and Therapeutics, Faculty of Medicine Diponegoro University.
Circ J. 2019 Mar 25;83(4):718-726. doi: 10.1253/circj.CJ-18-1088. Epub 2019 Feb 20.
Intracellular uric acid is known to increase the protein level and channel current of atrial Kv1.5; however, mechanisms of the uric acid-induced enhancement of Kv1.5 expression remain unclear.
The effects of uric acid on mRNA and protein levels of Kv1.5, as well as those of Akt, HSF1 and Hsp70, in HL-1 cardiomyocytes were studied by using qRT-PCR and Western blotting. The uptake of uric acid was measured using radio-labeled uric acid. The Kv1.5-mediated channel current was also measured by using patch clamp techniques. Uric acid up-taken by HL-1 cells significantly increased the level of Kv1.5 proteins in a concentration-dependent manner, with this increase abolished by an uric acid transporter inhibitor. Uric acid slowed degradation of Kv1.5 proteins without altering its mRNA level. Uric acid enhanced phosphorylation of Akt and HSF1, and thereby increased both transcription and translation of Hsp70; these effects were abolished by a PI3K inhibitor. Hsp70 knockdown abolished the uric acid-induced increases of Kv1.5 proteins and channel currents.
Intracellular uric acid could stabilize Kv1.5 proteins through phosphorylation of Akt and HSF1 leading to enhanced expression of Hsp70.
已知细胞内尿酸可增加心房 Kv1.5 的蛋白水平和通道电流；然而，尿酸诱导 Kv1.5 表达增强的机制仍不清楚。
通过 qRT-PCR 和 Western blot 研究尿酸对 HL-1 心肌细胞中 Kv1.5 的 mRNA 和蛋白水平以及 Akt、HSF1 和 Hsp70 的影响。使用放射性标记的尿酸测量尿酸的摄取。通过膜片钳技术测量 Kv1.5 介导的通道电流。HL-1 细胞摄取的尿酸可显著增加 Kv1.5 蛋白的水平，呈浓度依赖性，而尿酸转运蛋白抑制剂可消除这种增加。尿酸可减缓 Kv1.5 蛋白的降解而不改变其 mRNA 水平。尿酸可增强 Akt 和 HSF1 的磷酸化，从而增加 Hsp70 的转录和翻译；这些作用可被 PI3K 抑制剂所阻断。Hsp70 敲低可消除尿酸诱导的 Kv1.5 蛋白和通道电流的增加。
细胞内尿酸可通过 Akt 和 HSF1 的磷酸化稳定 Kv1.5 蛋白，从而增强 Hsp70 的表达。
Zotero 插件