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http://dx.doi.org/10.4062/biomolther.2021.087

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)
Publication Information
Biomolecules & Therapeutics / v.30, no.2, 2022 , pp. 145-150 More about this Journal
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.
Keywords
CPI-17; Fluoride; Galangin; MYPT1; Phorbol ester; ROCK;
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1 Amano, M., Ito, M., Kimura, K., Fukata, Y., Chihara, K., Nakano, T., Matsuura, Y. and Kaibuchi, K. (1996) Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J. Biol. Chem. 271, 20246-20249.   DOI
2 Ansari, H., Teng, B., Nadeem, A., Roush, K., Martin, K., Schnermann, J. and Mustafa, S. (2009) A1 adenosine receptor-mediated PKC and p42/p44 MAPK signaling in mouse coronary artery smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 297, H1032-H1039.   DOI
3 Gallet, C., Blaie, S., Levy-Toledano, S. and Habib, A. (2003) Thromboxane-induced ERK phosphorylation in human aortic smooth muscle cells. Adv. Exp. Med. Biol. 525, 71-73.   DOI
4 Hedges, J., Oxhorn, B., Carty, M., Adam, L., Yamboliev, I. and Gerthoffer, W. T. (2000) Phosphorylation of caldesmon by Erk MAP kinases in smooth muscle. Am. J. Physiol. Cell Physiol. 278, C718-C726.   DOI
5 Je, H. D. and Sohn, U. D. (2009) Inhibitory effect of genistein on agonist-induced modulation of vascular contractility. Mol. Cells 27, 191-198.   DOI
6 Johnson, R. P., El-Yazbi, A. F., Takeya, K., Walsh, E. J., Walsh, M. P. and Cole, W. C. (2009) Ca2+ sensitization via phosphorylation of myosin phosphatase targeting subunit at threonine-855 by Rho kinase contributes to the arterial myogenic response. J. Physiol. 587, 2537-2553.   DOI
7 Kim, J. I., Urban, M., Young, G. D. and Eto, M. (2012) Reciprocal regulation controlling the expression of CPI-17, a specific inhibitor protein for the myosin light chain phosphatase in vascular smooth muscle cells. Am. J. Physiol. Cell Physiol. 303, C58- C68.   DOI
8 Kitazawa, T., Eto, M., Woodsome, T. P. and Brautigan, D. L. (2000) Agonists trigger G protein-mediated activation of the CPI-17 inhibitor phosphoprotein of myosin light chain phosphatase to enhance vascular smooth muscle contractility. J. Biol. Chem. 275, 9897-9900.   DOI
9 Kuriyama, T., Tokinaga, Y., Tange, K., Kimoto, Y. and Ogawa, K. (2012) Propofol attenuates angiotensin II-induced vasoconstriction by inhibiting Ca2+-dependent and PKC-mediated Ca2+ sensitization mechanisms. J. Anesth. 26, 682-688.   DOI
10 Liu, Z. and Khalil, R. A. (2018) Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease. Biochem. Pharmacol. 153, 91-122.   DOI
11 Qiao, Y. N., He, W. Q., Chen, C. P., Zhang, C. H., Zhao, W., Wang, P., Zhang, L., Wu, Y. Z., Yang, X., Peng, Y. J., Gao, J. M., Kamm, K. E., Stull, J. T. and Zhu, M. S. (2014) Myosin phosphatase target subunit 1 (MYPT1) regulates the contraction and relaxation of vascular smooth muscle and maintains blood pressure. J. Biol. Chem. 289, 22512-22523.   DOI
12 Ren, K., Zhang, W., Wu, G., Ren, J., Lu, H., Li, Z. and Han, X. (2016) Synergistic anti-cancer effects of galangin and berberine through apoptosis induction and proliferation inhibition in oesophageal carcinoma cells. Biomed. Pharmacother. 84, 1748-1759.   DOI
13 Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. (2003) Ca2+-dependent activation of Rho and Rho kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res. 93, 548-556.   DOI
14 Somlyo, A. P. and Somlyo, A. V. (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev. 83, 1325-1358.   DOI
15 Tsai, M. H. and Jiang, M. J. (2006) Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle contraction. Pflugers Arch. 453, 223-232.   DOI
16 Qi, F., Ogawa, K., Tokinaga, Y., Uematsu, N., Minonishi, T. and Hatano, Y. (2009) Volatile anesthetics inhibit angiotensin II-induced vascular contraction by modulating myosin light chain phosphatase inhibiting protein, CPI-17 and regulatory subunit, MYPT1 phosphorylation. Anesth. Analg. 109, 412-417.   DOI
17 Aloud, A. A., Chinnadurai, V., Govindasamy, C., Alsaif, M. A. and AlNumair, K. S. (2018) Galangin, a dietary flavonoid, ameliorates hyperglycaemia and lipid abnormalities in rats with streptozotocin-induced hyperglycaemia. Pharm. Biol. 56, 302-308.   DOI
18 Cao, J., Wang, H., Chen, F., Fang, J., Xu, A., Xi, W., Zhang, S., Wu, G. and Wang, Z. (2016) Galangin inhibits cell invasion by suppressing the epithelial-mesenchymal transition and inducing apoptosis in renal cell carcinoma. Mol. Med. Rep. 13, 4238-4244.   DOI
19 Goyal, R., Mittal, A., Chu, N., Shi, L., Zhang, L. and Longo, L. D. (2009) Maturation and the role of PKC-mediated contractility in ovine cerebral arteries. Am. J. Physiol. Heart Circ. Physiol. 297, H2242-H2252.   DOI
20 Jeon, S. B., Jin, F., Kim, J. I., Kim, S. H., Suk, K., Chae, S. C., Jun, J. E., Park, W. H. and Kim, I. K. (2006) A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochem. Biophys. Res. Commun. 343, 27-33.   DOI
21 Zha, W. J., Qian, Y., Shen, Y., Du, Q., Chen, F. F., Wu, Z. Z., Li, X. and Huang, M. (2013) Galangin abrogates ovalbumin-induced airway inflammation via negative regulation of NF-κB. Evid. Based Complement. Alternat. Med. 2013, 767689.
22 Sasahara, T., Okamoto, H., Ohkura, N., Kobe, A. and Yayama, K. (2015) Epidermal growth factor induces Ca2+ sensitization through Rho-kinase-dependent phosphorylation of myosin phosphatase target subunit 1 in vascular smooth muscle. Eur. J. Pharmacol. 762, 89-95.   DOI
23 Zhang, H. T., Wu, J., Wen, M., Su, L. J. and Luo, H. (2012) Galangin induces apoptosis in hepatocellular carcinoma cells through the caspase 8/t-Bid mitochondrial pathway. J. Asian Nat. Prod. Res. 14, 626-633.   DOI
24 Kim, H. H., Bae, Y. and Kim, S. H. (2013) Galangin attenuates mast cell-mediated allergic inflammation. Food Chem. Toxicol. 57, 209-216.   DOI
25 Devadoss, D., Ramar, M. and Chinnasamy, A. (2018) Galangin, a dietary flavonol inhibits tumor initiation during experimental pulmonary tumorigenesis by modulating xenobiotic enzymes and antioxidant status. Arch. Pharm. Res. 41, 265-275.   DOI
26 Wilson, D. P., Susnjar, M., Kiss, E., Sutherland, C. and Walsh, M. P. (2005) Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem. J. 389, 763-774.   DOI
27 Wooldridge, A. A., MacDonald, J. A., Erdodi, F., Ma, C., Borman, M. A., Hartshorne, D. J. and Haystead, T. A. (2004) Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J. Biol. Chem. 279, 34496-34504.   DOI
28 Yang, Q., Fujii, W., Kaji, N., Kakuta, S., Kada, K., Kuwahara, M., Tsubone, H., Ozaki, H. and Hori, M. (2018) The essential role of phospho-T38 CPI-17 in the maintenance of physiological blood pressure using genetically modified mice. FASEB J. 32, 2095-2109.   DOI