Molecular mechanisms of action of Laennec against development of metabolic syndrome and obesity


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Metabolic syndrome (MS) is a complex of metabolic disorders, leading to an increased risk for cardiovascular diseases and diabetes. MS components include abdominal obesity, arterial hypertension, specific disorders of lipid and carbohydrate metabolism. This article presents the results of a systematic analysis of the molecular mechanisms of the action of the peptide components of the Laennec on the pathophysiological components of MS. Laennec peptides counteract development of MS by: 1) increasing cell survival (cytoprotection), 2) restoring the sensitivity of cells to glucose and eliminating insulin resistance, 3) reducing elevated blood pressure, 4) eliminating dyslipidemia, reducing fatty infiltration and restoring liver function, 5) anti-inflammatory and 6) antioxidant action.

Full Text

Restricted Access

About the authors

Olga A. Gromova

Ivanovo state medical academy

Email: unesco.gromova@gmail.com
MD, professor of the Department of pharmacology and clinical pharmacology

Ivan Yu. Torshin

Moscow institute of physics and technology (state university)

candidate of physico-mathematical sciences, associate professor of the Department of intelligent systems

Viktor G. Zgoda

V.N. Orehovich Scientific Research Institute of Biomedical Chemistry

doctor of biology, head of the Department of systemic biology

Irina K. Tomilova

Ivanovo state medical academy

MD, head of the Department of biochemistry

References

  1. Громова О.А., Торшин И.Ю., Гилельс А.В., Диброва Е.А., Гришина Т.Р., Волков А.Ю., Лиманова О.А., Назаренко О.А., Калачева А.Г., Демидов В.И. Препараты плаценты человека: фундаментальные и клинические исследования. Врач. 2014;4:67- 72. [Gromova O.A., Torshin I.Yu., Gilels A.V., Dibrova Ye.A., Grishina T.R., Volkov A.Yu., Limanova O.A., Nazarenko O.A., Kalacheva A.G., Demidov V.I. Preparations of human placenta: basic science and clinical research. Doctor. 2014;4:67-72 (in Russ.)]
  2. Торшин И.Ю., Громова О.А., Диброва Е.А., Марусич Е.И., Гилельс А.В., Гришина Т.Р., Назаренко О.А., Демидов В.И., Касяник М.С. Гидролизат плаценты человека в составе препарата Лаеннек снижает выраженность маркеров старения in vitro и in vivo. Эстетическая медицина. 2017;1. [Torshin I.Yu., Gromova O.A., Dibrova Ye.A., Marusich Ye.I., Gilels A.V., Grishina T.R., Nazarenko O.A., Demidov V.I., Kasyanik M.C. Human placenta extract in the composition of the drug Laennec reduces the severity markers of senescence in vitro and in vivo. Aesthetic medicine. 2017;1 (in Russ.)]
  3. Леонов С.В., Марусич Е.И., Громова О.А., Торшин И.Ю., Диброва Е.А. Антивозрастной эффект гидролизата плаценты человека. Доказательный стандарт. Терапия. 2017;4:75-83. [Leonov S.V., Marusich Ye.I., Gromova O.A., Torshin I.Yu., Dibrova Ye.A. Anti-aging effect of human placenta hydrolysate. Evidence-based standard. Therapy. 2017;4:75-83 (in Russ.)]
  4. Liu K.X., Kato Y., Kaku T., Sugiyama Y. Human placental extract stimulates liver regeneration in rats. Biol. Pharm. Bull. 1998;21(1):44-9.
  5. Минушкин О.Н., Калинин А.В., Масловский Л.В., Васильев А.П., Квасовка В.В., Дубовая Т.К., Батурина Г.А., Зверков И.В. Лаеннек: опыт внутривенного капельного введения при лечении некоторых диффузных заболеваний печени. Клинические перспективы гастроэнтерологии, гепатологии. 2005;2:27-30. [Minushkin O.N., Kalinin A.V., Maslovsky L.V., Vasiliev A.P., Kvasovka V.V., Dubovaya T.K., Baturina G.A., Zverkov I.V. Laennec: experience of intravenous infusion in the treatment of some diffuse diseases of the liver. Clinical prospects of gastroenterology, hepatology. 2005;2:27-30 (in Russ.)]
  6. Nakayama S., Kodama K., Oguchi K. A comparative study of human placenta hydrolysate (Laennec) by intravenous or subcutaneous injection on liver regeneration after partial hepatectomy in normal and CCl4-induced cirrhosis rats. Nippon Yakurigaku Zasshi. 1989;94(5):289-97.
  7. Торшин И.Ю., Згода В.Г., Громова О.А., Баранов И.И., Демидов В.И., Назаренко О.А., Сотникова Н.Ю., Каримова И.М. Анализ легкой пептидной фракции Лаеннека методами современной протеомики. Фармакокинетика и фармакодинамика. 2016;4:31-42. [Torshin I.Yu., Zgoda V.G., Gromova O.A., Baranov I.I., Demidov V.I., Nazarenko O.A., Sotnikova N.Yu., Karimova I.M. Analysis of light peptide fraction of Laennec by methods of modern proteomics. Pharmacokinetics and pharmacodynamics. 2016;4:31-42 (in Russ.)]
  8. Назаренко О.А., Громова О.А., Демидов В.И., Торшин И.Ю., Томилова И.К., Алексахина Е.Л. Сравнительная оценка хронической перегрузки железом при применении препаратов железа в субтоксических дозах. Терапия. 2016;6:82-8. [Nazarenko O.A., Gromova O.A., Demidov V.I., Torshin I.Yu, Tomilova I.K., Aleksakhina Ye.L. Comparative evaluation of chronic iron overload in the application of iron preparations in the sub-toxic doses. Therapy. 2016;6:82-8 (in Russ.)]
  9. Громова О.А., Торшин И.Ю., Минушкин О.Н., Диброва Е.А., Каримова И.М., Кустова Е.В. Об эффективности и молекулярных меха низмах действия препарата Лаеннек в лечении патологических состояний печени, связанных с отложением железа в печени. Медицинский журнал «Дело жизни». 2015;1(1):44-51. [Gromova O.A., Torshin I.Yu., Minushkin O.N., Dibrova Ye.A., Karimova I.M., Kustova Ye.V. On the efficiency and molecular mechanisms of action of the drug Laennec in treatment of pathological conditions of the liver associated with iron deposition in the liver. Medical journal «Business of life». 2015;1(1):44-51 (in Russ.)]
  10. Torshin I.Yu., Rudakov K.V. On metric spaces arising during formalization of problems of recognition and classification. Part 2: Density properties. Pattern Recognition and Image Analysis. 2016;26(3):483-96.
  11. Torshin I.Yu., Rudakov K.V. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 1: Factorization approach. Pattern Recognition and Image Analysis. 2017;27(1):16-28.
  12. Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. USA. 2008;105(31):10762-7.
  13. Frasca D., Diaz A., Romero M., Vazquez T., Blomberg B.B. Obesity induces pro-inflammatory B cells and impairs B cell function in old mice. Mech. Ageing Dev. 2017;162:91-9.
  14. Guo Z., Dai B., Jiang T., Xu K., Xie Y., Kim O., Nesheiwat I., Kong X., Melamed J., Handratta V.D., Njar V.C., Brodie A.M., Yu L.R., Veenstra T.D., Chen H., Qiu Y. Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell. 2006;10(4):309-19.
  15. Mahajan N.P., Liu Y., Majumder S., Warren M.R., Parker C.E., Mohler J.L., Earp H.S., Whang Y.E. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation. Proc. Natl. Acad. Sci. USA. 2007;104(20):8438-43.
  16. Werz O., Szellas D., Steinhilber D., Radmark O. Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). J. Biol. Chem. 2002;277(17):14793-800.
  17. Fiore M., Forli S., Manetti F. Targeting Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts To Lead Small Molecule Inhibitors to Clinical Trials. J. Med. Chem. 2016;59(8):3609-34.
  18. Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., Mohammed S. Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome. Res. 2013;12(1):260-71.
  19. Demarchi F., Bertoli C., Sandy P., Schneider C. Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 stability. J. Biol. Chem. 2003;278(41):39583-90.
  20. Jho Eh, Lomvardas S., Costantini F. A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression. Biochem. Biophys. Res. Commun. 1999;266(1):28-35.
  21. Jope R.S., Johnson G.V. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem. Sci. 2004;29(2):95-102.
  22. Wang L., Lin H.K., Hu Y.C., Xie S., Yang L., Chang C. Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells. J. Biol. Chem. 2004;279(31):32444-52.
  23. Singh S.P., Tao S., Fields T.A., Webb S., Harris R.C., Rao R. Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia-reperfusion in mice. Dis. Model Mech. 2015;8(8):931-40.
  24. Zheng J., Liu Z., Li W., Tang J., Zhang D., Tang X. Lithium posttreatment confers neuroprotection through glycogen synthase kinase-3beta inhibition in intracerebral hemorrhage rats. J. Neurosurg. 2016;1-9.
  25. Jope R.S., Yuskaitis C.J., Beurel E. Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem. Res. 2007;32(4-5):577-95.
  26. Bhushan B., Poudel S., Manley M.W. Jr, Roy N., Apte U. Inhibition of glycogen synthase kinase 3 accelerated liver regeneration after acetaminophen-induced hepatotoxicity in mice. Am. J. Pathol. 2017;187(3):543-52.
  27. Huang J., Guo X., Li W., Zhang H. Activation of Wnt/beta-catenin signalling via GSK3 inhibitors direct differentiation of human adipose stem cells into functional hepatocytes. Sci. Rep. 2017;7:40716.
  28. Nagata M., Nakamura T., Hata Y., Yamaguchi S., Kaku T., Kinoshita S. JBP485 promotes corneal epithelial wound healing. Sci. Rep. 2015;5:14776.
  29. Liu T., Guo X., Meng Q., Wang C., Liu Q., Sun H., Ma X., Kaku T., Liu K. Effect of JBP485 on obstructive jaundice is related to regulation of renal Oat1, Oat3 and Mrp2 expression in ANIT-treated rats. Peptides. 2012;36(1):78-85.
  30. Wu J., Wang C., Liu Q., Yang T., Zhang Q., Peng J., Gao Y., Sun H., Kaku T., Liu K. Protective effect of JBP485 on concanavalin A-induced hepatocyte toxicity in primary cultured rat hepatocytes. Eur. J. Pharmacol. 2008;589(1-3):299-305.
  31. Yang T., Wu J., Wang C., Liu Q., Ma X., Peng J., Kaku T., Liu K. Protective effect of JBP485 on concanavalin A-induced liver injury in mice. J. Pharm. Pharmacol. 2009;61(6):767-74.
  32. Wu A., Grant D.B., Hambley J., Levi A.J. Reduced serum somatomedin activity in patients with chronic liver disease. Clin. Sci. Mol. Med. 1974;47(4):359-66.
  33. Vera M., Sobrevals L., Zaratiegui M., Martinez L., Palencia B., Rodriguez C.M., Prieto J., Fortes P. Liver transduction with a simian virus 40 vector encoding insulin-like growth factor I reduces hepatic damage and the development of liver cirrhosis. Gene Ther. 2007;14(3):203-10.
  34. Sobrevals L., Rodriguez C., Romero-Trevejo J.L., Gondi G., Monreal I., Paneda A., Juanarena N., Arcelus S., Razquin N., Guembe L., Gonzalez-Aseguinolaza G., Prieto J., Fortes P. Insulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesis leading to cirrhosis reversion in rats. Hepatology. 2010;51(3):912-21.
  35. Tutau F., Rodriguez-Ortigosa C., Puche J.E., Juanarena N., Monreal I., Garcia Fernandez M., Clavijo E., Castilla A., Castilla-Cortazar I. Enhanced actions of insulin-like growth factor-I and interferon-alpha co-administration in experimental cirrhosis. Liver Int. 2009;29(1):37-46.
  36. Kling P.J., Taing K.M., Dvorak B., Woodward S.S., Philipps A.F. Insulin-like growth factor-I stimulates erythropoiesis when administered enterally. Growth Factors. 2006;24(3):218-23.
  37. Zivna H., Zivny P., Vokurkova D., Svejkovska K., Palicka V. The effect of chronic iron losses on liver regeneration in male and female rats. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2010;154(2):153-8.
  38. Garcia-Fernandez M., Castilla-Cortazar I., Diaz-Sanchez M., Navarro I., Puche J.E., Castilla A., Casares A.D., Clavijo E., Gonzalez-Baron S. Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis. BMC Gastroenterol. 2005;5:7.
  39. Clemmons D.R. The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J. Clin. Invest. 2004;113(1):25-7.
  40. Roof S.R., Boslett J., Russell D., del Rio C., Alecusan J., Zweier J.L., Ziolo M.T., Hamlin R., Mohler P.J., Curran J. Insulin-like growth factor 1 prevents diastolic and systolic dysfunction associated with cardiomyopathy and preserves adrenergic sensitivity. Acta. Physiol. (Oxf). 2016;216(4):421-34.
  41. De Lorenzo A., Moreira A.S., Souza E.G., Oliveira G.M. Insulin-like growth factor-1 in early-onset coronary artery disease: Insights into the pathophysiology of atherosclerosis. Int. J. Cardiol. 2016;202:1-2.
  42. Wang C.Y., Li X.D., Hao Z.H., Xu D. Insulin-like growth factor-1 improves diabetic cardiomyopathy through antioxidative and antiinflammatory processes along with modulation of Akt/GSK-3beta signaling in rats. Korean J. Physiol. Pharmacol. 2016;20(6):613-9.
  43. Li X.M., Ferraro L., Tanganelli S., O'Connor W.T., Hasselrot U., Ungerstedt U., Fuxe K. Neurotensin peptides antagonistically regulate postsynaptic dopamine D2 receptors in rat nucleus accumbens: a receptor binding and microdialysis study. J. Neural. Transm. Gen. Sect. 1995;102(2):125-37.
  44. Gendron L., Perron A., Payet M.D., Gallo-Payet N., Sarret P., Beaudet A. Low-affinity neurotensin receptor (NTS2) signaling: internalization-dependent activation of extracellular signal-regulated kinases 1/2. Mol. Pharmacol. 2004;66(6):1421-30.
  45. Toda M., Suzuki T., Hosono K., Kurihara Y., Kurihara H., Hayashi I., Kitasato H., Hoka S., Majima M. Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis. Biomed. Pharmacother. 2008;62(6):352-9.
  46. Leventoglu S., Koksal H., Sancak B., Taneri F., Onuk E. The effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with experimental obstructive jaundice. J. Hepatobiliary Pancreat. Surg. 2009;16(4):546-51.
  47. Bar-Or D., Rael L.T., Lau E.P., Rao N.K., Thomas G.W., Winkler J.V., Yukl R.L., Kingston R.G., Curtis C.G. An analog of the human albumin N-terminus (Asp-Ala-His-Lys) prevents formation of copper-induced reactive oxygen species. Biochem. Biophys. Res. Commun. 2001;284(3):856-62.
  48. Konitsiotis A.D., Raynal N., Bihan D., Hohenester E., Farndale R.W., Leitinger B. Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen. J. Biol. Chem. 2008;283(11):6861-8.
  49. Carafoli F., Bihan D., Stathopoulos S., Konitsiotis A.D., Kvansakul M., Farndale R.W., Leitinger B., Hohenester E. Crystallographic insight into collagen recognition by discoidin domain receptor 2. Structure. 2009;17(12):1573-81.
  50. Vogel W.F., Abdulhussein R., Ford C.E. Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal. 2006;18(8):1108-16.
  51. Potenza M.V., Mechanick J.I. The metabolic syndrome: definition, global impact, and pathophysiology. Nutr. Clin. Pract. 2009;24(5):560-77.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies