Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2014; 60(3): 3-10

Effect of quercetin on proteasome activity in the aorta and heart tissues of spontaneously hypertensive rats

Honcharov SV, Portnichenko HV, Tumanovs'ka LV, Pashevin DO, Kuz'menko MO, Moĭbenko OO, Dosenko VIe.

    O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine


To determine the role of proteasome proteolysis in the pathogenesis of hypertension, we have studied the proteolytic activity of the proteasome in the aorta and heart tissues of rats with spontaneous hypertension (line SHR), and used quercetin, the drug that can inhibit the activity of this multicatalytic complex. In the aorta of SHR, the activities of the proteasome were not significantly different from that observed in Wistar rats. At the same time, in the heart tissues the trypsin-like (at 40 %, P > 0.05), and chymotrypsin-like (by 1,7 times, P < 0.03) activities were significantly less in SHR. significant morphological changes (fibrosis of the left ventricle was 4.7 %, aorta intima width was increased and heart weight index was higher by 21,6 % (3,7 ± 0,6 mg/g) compared with Wistar rats (2,9 ± 0,4 mg/g, P < 0.004) were observed in these animals functional disorders (reduced stroke volume by 3 times (P < 0.0001), ejection fraction by 2.5 times (P < 0.0001), increased end diastolic pressure by 6.5 times (P < 0.005), end systolic pressure by 15 % (P < 0.004)) were revealed. Pharmacological drug “Qvercetin” effectively inhibited trypsin-like and chymotrypsin-like proteasome activities Вплив кверцетину на протеасомну активність в аорті та серці щурів ISSN 0201-8489 Фізіол. журн., 2014, Т. 60, № 3 9 in the aorta (2.7-fold (P < 0.005) and 2-fold (Р<0,003), correspondingly) and trypsin-like, and peptidyl-glutamyl peptide-hydrolyzing-like activities (2.4 -fold, P > 0.05 and 9.3- fold, P < 0.02, correspondingly) activities in the heart, leading to a significant improvement of morphological and functional parameters of the heart. Whereas the drug “Qvercetin” that is widely used in clinical practice (especially in therapy of acute myocardial infarction) it could be recommended for the use in prevention of cardiac remodeling with high level of blood pressure.

Keywords: proteasome activity, arterial hypertension, aorta,heart, quercetin.


  1. Okamoto H, Takaoka M, Ohkita M, Itoh M, Nishioka M,Matsumura Y. A proteasome inhibitor lessens the increased aortic endothelin-1 content in deoxycorticosterone acetate-salt hypertensive rats. Eur J Pharmacol. 1998;350(1):11-2. CrossRef  
  2. Takaoka M, Ohkita M, Itoh M, Kobayashi Y, Okamoto H, Matsumura Y. A proteasome inhibitor prevents vascular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats. Clin Exp Pharmacol Physiol. 2001; 28(5-6):466-8. CrossRef PubMed
  4. Takaoka M, Okamoto H, Ito M, Nishioka M, Kita S, Matsumura Y: Antihypertensive effect of a proteasome inhibitor in DOCA-salt hypertensive rats. Life Sci. 1998;63(4): 65-70. CrossRef  
  5. Pashevin DO, Dosenko BIe, Byts' IuV, Moibenko OO. Antiatherogenic characteristics of korvitin: effect on proteasome activity of the aorta, heart, and blood cells. Fiziol Zh. 2009; 55(4): 50-7. PubMed
  7. Xu J, Wang S, Zhang M, Wang Q, Asfa S, Zou MH. Tyrosine nitration of PA700 links proteasome activation to endothelial dysfunction in mouse models with cardiovascular risk factors. PLoS One. 2012; 7(1): 29649. CrossRef PubMed PubMedCentral
  9. Tanaka K. Molecular mechanism of immunological recognition and the abnormality. Nihon Rinsho. 1997; 55(6):1356-62. PubMed
  11. Ying WZ, Sanders PW. Accelerated ubiquitination and proteasome degradation of a genetic variant of inducible nitric oxide synthase. Biochem J. 2003; 376: 789-94. CrossRef PubMed PubMedCentral
  13. Romero M, Jimenez R, Hurtado B, Moreno JM, Rodriguez- Gomez I, Lopez-Sepulveda R, Zarzuelo A, Perez- Vizcaino F, Tamargo J, Vargas F, Duarte J. Lack of beneficial metabolic effects of quercetin in adult spontaneously hypertensive rats. Eur J Pharmacol. 2010; 627(1-3): 242-50. CrossRef PubMed
  15. Pashevin DA, Tumanovska LV, Dosenko VE, Nagibin VS,Gurianova VL, Moibenko AA. Antiatherogenic effect of quercetin is mediated by proteasome inhibition in the aorta and circulating leukocytes. Pharmacol Rep. 2011;63(4): 1009-18. CrossRef  
  16. Dosenko VE, Nagibin VS, Tumanovskaia LV, Zagorii VIu, Moibenko AA. The influence of quercetin on the activity of purified 20S, 26S proteasome and proteasomal activity in isolated cardiomyocytes. Biomed Khim. 2006; 52(2):138-45. PubMed
  18. Nam S., Smith DM., Dou QP. Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo. J. Biol. Chem. 2001; 276(16): 13322-30. CrossRef PubMed
  20. Gaczynska M, Goldberg AL, Tanaka K, Hendil KB, Rock KL. Proteasome subunits X and Y alter peptidase activities in opposite ways to the interferon-gammainduced subunits LMP2 and LMP7. J Biol Chem. 1996;271(29):17275-80. CrossRef PubMed
  22. Duarte J, Raquel P-P,Vargas F, Ocete M, Francisco P-V, Zarzuelo A, Tamargo J.ò Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats.Br. J. Pharmacol. 2001; 133: 117-124. CrossRef PubMed PubMedCentral
  24. Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell. 2012; 148(4): 727-38. CrossRef PubMed
  26. Wisse BE: The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity.J Am Soc Nephrol. 2004; 15(11): 2792-800. CrossRef PubMed
  28. Tilahun AY, Theuer JE, Patel R, David CS, Rajagopalan G.Detrimental effect of the proteasome inhibitor, bortezomib in bacterial superantigen- and lipopolysaccharideinduced systemic inflammation. Mol. Ther. 2010;18(6):1143-54. CrossRef PubMed PubMedCentral
  30. Bockorny M, Chakravarty S, Schulman P, Bockorny B, Bona R. Severe heart failure after bortezomib treatment in a patient with multiple myeloma: a case report and review of the literature. Acta Haematol. 2012;128(4): 244-7. CrossRef PubMed
  32. Takagaki M, McCarthy PM, Chung M, Connor J, Dessoffy R, Ochiai Y, Howard M, Doi K, Kopcak M, Mazgalev TN, Fukamachi K. Preload-adjusted maximal power: a novel index of left ventricular contractility in atrial fibrillation. Heart. 2002; 88(2): 170-6. CrossRef PubMed PubMedCentral
  34. Aviram M, Fuhrman B. Wine flavonoids protect against LDL oxidation and atherosclerosis. Ann N Y Acad Sci. 2002; 957:146-61. CrossRef PubMed
  36. Hollman PC, Katan MB. Bioavailability and health effects of dietary flavonols in man. Arch Toxicol Suppl. 1998;20: 237-48. CrossRef  
  37. Ishizawa K, Yoshizumi M, Kawai Y, Terao J, Kihira Y, Ikeda Y, Tomita S, Minakuchi K, Tsuchiya K, Tamaki T.Pharmacology in health food: metabolism of quercetin in vivo and its protective effect against arteriosclerosis.J Pharmacol Sci. 2011;115(4): 466-70. CrossRef PubMed
  39. Haibo Xu, Elizabeth B. Oliveira-Sales, Fiona McBride, Beihui Liu, James Hewinson, Marie Toward, Emma B.Hendy, Delyth Graham, Anna F. Dominiczak, Monica Giannotta, Hidefumi Waki,Raimondo Ascione, Julian F.R. Paton, Sergey Kasparov. Upregulation of junctional adhesion molecule-A is a putative prognostic marker of hypertension. Cardiovasc Res. 2012; 96(3): 552-60. CrossRef PubMed PubMedCentral
  41. Waki H., Hendy E.B., Hindmarch C.C., Gouraud S., Toward M., Kasparov S., Murphy D., Paton J.F. Excessive leukotriene B4 in nucleus tractus solitarii is prohypertensive in spontaneously hypertensive rats. Hypertension.2013; 61(1):194-201. CrossRef PubMed PubMedCentral
  43. Christman JW, Lancaster LH, Blackwell TS. Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med. 1998; 24(11):1131-8. CrossRef PubMed
  45. Gonzalez MA, Selwyn AP. Endothelial function,inflammation, and prognosis in cardiovascular disease.Am J Med. 2003; 115:99-106. CrossRef  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.