Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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The Effect of Galangin on the Regulation of Vascular Contractility via the Holoenzyme Reactivation Suppressing ROCK/CPI-17 rather than PKC/CPI-17

  • Yoon, Hyuk-Jun (Department of Pharmacology, College of Pharmacy, Daegu Catholic University) ;
  • Jung, Won Pill (Department of Pharmacology, College of Pharmacy, Daegu Catholic University) ;
  • Min, Young Sil (Department of Pharmaceutical Science, Jungwon University) ;
  • Jin, Fanxue (Department of Pharmacology, Kyungpook National University School of Medicine) ;
  • Bang, Joon Seok (College of Pharmacy, Sookmyung Women's University) ;
  • Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Je, Hyun Dong (Department of Pharmacology, College of Pharmacy, Daegu Catholic University)
  • Received : 2021.05.03
  • Accepted : 2021.06.18
  • Published : 2022.03.01
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Abstract

In this study, we investigated the influence of galangin on vascular contractibility and to determine the mechanism underlying the relaxation. Isometric contractions of denuded aortic muscles were recorded and combined with western blot analysis which was performed to measure the phosphorylation of phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) and to evaluate the effect of galangin on the RhoA/ROCK/CPI-17 pathway. Galangin significantly inhibited phorbol ester-, fluoride- and thromboxane mimetic-induced vasoconstrictions regardless of endothelial nitric oxide synthesis, suggesting its direct effect on vascular smooth muscle. Galangin significantly inhibited the fluoride-dependent increase in pMYPT1 and pCPI-17 levels and phorbol 12,13-dibutyrate-dependent increase in pERK1/2 level, suggesting repression of ROCK and MEK activity and subsequent phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that galangin-induced relaxation involves myosin phosphatase reactivation and calcium desensitization, which appears to be mediated by CPI-17 dephosphorylation via not PKC but ROCK inactivation.

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References

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