Zinc Increases ABCA1 by Attenuating Its Clearance Through the Modulation of Calmodulin Activity

• Lu Rui

  Food and Nutritional Sciences,Chubu University

• Ishikawa Takahiro

  Food and Nutritional Sciences,Chubu University

• Tanaka Mamoru

  Food and Nutritional Sciences,Chubu University

• Tsuboi Tomoe

  Food and Nutritional Sciences,Chubu University

• Yokoyama Shinji

  Food and Nutritional Sciences,Chubu University

抄録

Aim: We previously revealed that Ca^＋＋-activated calmodulin binds to ABCA1 by the region near the PEST sequence and retards its calpain-mediated degradation to increase HDL biogenesis. Calmodulin activity is reportedly modulated also by other nutritional divalent cations; thus, we attempted to determine whether Zn^＋＋ is involved in the regulation of ABCA1 stability through the modulation of calmodulin activity. Methods: The effects of Zn^＋＋ on ABCA1 expression was investigated in J774 mouse macrophage cell-line cells and HepG2 human hepatoma cell-line cells. Results: Zn^＋＋ increased ABCA1 expression, not by increasing the mRNA but by attenuating its decay rate, more prominently in the presence of cAMP. Accordingly, it enhanced cell cholesterol release with extracellular apolipoprotein A-I. Calmodulin binding to ABCA1 was increased by Zn^＋＋ and Ca^＋＋. Zn^＋＋ suppressed calpain-mediated hydrolysis of the peptide of ABCA1 cytosolic loop, including the PEST sequence and the calmodulin-binding site, in a calmodulin- dependent fashion, in the presence of the minimum amount of Ca^＋＋ to activate calpain, but not calmodulin. Calpain activity was not directly inhibited by Zn^＋＋ at the concentration for enhancing calmodulin binding to ABCA1. Conclusion: Nutritional divalent cation Zn^＋＋ is involved in the regulation of ABCA1 activity and biogenesis of HDL through the modulation of calmodulin activity. The results were consistent with previous clinical findings that Zn^＋＋ increased plasma HDL in the conditions of sympathetic activation, such as type 2 diabetes and chronic hemodialysis.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ

  Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ 28 (3), 261-270, 2021-03-01

  一般社団法人 日本動脈硬化学会

キーワード

• Zinc
• ATP binding cassette transporter A1
• Calmodulin
• Calpain
• High density lipoprotein

詳細情報

• CRID: 1390287297545633152
• NII論文ID: 130007993133
• DOI: 10.5551/jat.55384
• ISSN: 18803873
• ISSN: 13403478
• PubMed: 32581187
• Web Site: https://www.jstage.jst.go.jp/article/jat/28/3/28_55384/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2021325969
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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