Uric Acid-Induced Enhancements of Kv1.5 Protein Expression and Channel Activity via the Akt-HSF1-Hsp70 Pathway in HL-1 Atrial Myocytes

• Taufiq Fikri

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Maharani Nani

  Department of Pharmacology and Therapeutics, Faculty of Medicine Diponegoro University

• Li Peili

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Kurata Yasutaka

  Department of Physiology II, Kanazawa Medical University Faculty of Medicine

• Ikeda Nobuhito

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Kuwabara Masanari

  Department of Cardiology, Toranomon Hospital

• Otani Naoyuki

  Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine

• Miake Junichiro

  Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine

• Hasegawa Akira

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Tsuneto Motokazu

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Shirayoshi Yasuaki

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

• Ninomiya Haruaki

  Department of Biological Regulation, Tottori University

• Saitoh Tatsuya

  Division of Inflammation Biology, Institute for Enzyme Research, Tokushima University Laboratory of Bioresponse Regulation, Graduate School of Pharmaceutical Sciences, Osaka University

• Nakai Akira

  Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine

• Yamamoto Kazuhiro

  Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine

• Hisatome Ichiro

  Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science

Abstract

Background: 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. Methods and Results: 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. Conclusions: Intracellular uric acid could stabilize Kv1.5 proteins through phosphorylation of Akt and HSF1 leading to enhanced expression of Hsp70.

Journal

• Circulation Journal

  Circulation Journal 83 (4), 718-726, 2019-03-25

  The Japanese Circulation Society

Keywords

• Akt
• Heat shock factor 1
• Heat shock protein 70
• Kv1.5
• Uric acid

Details

• CRID: 1390564238092368768
• NII Article ID: 40021855828
• NII Article ID: 130007620506
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-18-1088
• ISSN: 13474820
• ISSN: 13469843
• NDL BIB ID: 029609547
• PubMed: 30787218
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I029609547
• Web Site: https://www.jstage.jst.go.jp/article/circj/83/4/83_CJ-18-1088/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2019305051
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed