Biological Functions of Succinate (a Review of Foreign Experimental Studies)
Abstract
The published data on the modern concept of the biological role of succinate, an intermediate of the citric acid cycle are analysed in the review. Special interest to succinate is determined by investigations on the mitochondrial functions at different pathologies, discovery of the hypoxia-inducible factor HIF-1 and studies on the human genome, that resulted in detection of the G-protein coupled receptors, which selectively are bound with succinate. According to the published experimental data, besides participation in oxidative reactions, succinate is considered as a key contributor to physiological, metabolic and genetic processes.
About the Authors
V. V. Valeev
Scientific and Technological Pharmaceutical Firm «POLYSAN»
Russian Federation
Russian Federation
A. L. Kovalenko
Institute of Toxicology, Federal Medico-Biological Agency
Russian Federation
Russian Federation
E. V. Talikova
Sankt-Petersburg Medical-Social Institute
Russian Federation
Russian Federation
V. A. Zaplutanov
Sankt-Petersburg State Chemico-Pharmaceutical Academy
Russian Federation
Russian Federation
T. Yu. Delvig-Kamenskaya
Sankt-Petersburg State Chemico-Pharmaceutical Academy
Russian Federation
Russian Federation
References
1. Mills E., O'Neill L.A. Succinate: a metabolic signal in inflammation. Trends Cell Biol 2014; 24; 5: 313-320.
2. Ariza A.C., Deen P.M., Robben J.H. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions. Front Endocrinol (Lausanne) 2012; 3: 22.
3. Chen T.T., Maevsky E.I., Uchite M.L. Maintenance of homeostasis in the aging hypothalamus: the central and peripheral roles of succinate. Front Endocrinol (Lausanne) 2015; 6: 7.
4. Биохимия: учебник / Под ред. Е.С. Северина. 5-е изд. М, ГЭОТАР-Медиа 2011. / Biohimija: uchebnik / Pod red. E.S. Severina. 5-e izd. M, GJeOTAR-Media 2011. [in Russian]
5. Brealey D., Brand M., Hargreaves I. et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 2002; 360: 9328: 219-223.
6. Protti A., Carre J., Frost M. et al. Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle. Crit Care Med 2007; 35: 9: 2150-2155.
7. Singer M. The role of mitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence 2014; 5: 1: 66-72.
8. Malaisse W.J., Nadi A.B., Ladriere L. et al. Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia. Nutrition 1997; 13: 330-341.
9. Ferreira F.L., Ladriere L., Vincent J.L. et al. Prolongation of survival time by infusion of succinic acid dimethyl ester in a caecal ligation and perforation model of sepsis. Horm Metab Res 2000; 32: 335-336.
10. Cairns C.B., Ferroggiaro A.A., Walther J.M. et al. Postischemic administration of succinate reverses the impairment of oxidative phosphorylation after cardiac ischemia and reperfusion injury. Circulation 1997; 96: 9: Suppl: 260-265.
11. Sakamoto M., Takeshige K., Yasui H., Tokunaga K. Cardioprotective effect of succinate against ischemia / reperfusion injury. Surg Today 1998; 28: 5: 522-528.
12. Weinberg J.M., Venkatachalam M.A., Roeser N.F., Saikumar P. et al. Anaerobic and aerobic pathways for salvage of proximal tubules from hypoxia-induced mitochondrial injury. Am J Physiol Renal Physiol 2000; 279: 5: F927-943.
13. Гривенникова В.Г., Виноградов А.Д. Генерация активных форм кислорода митохондриями. Успех биол хим 2013; 53: 245-296.
14. Гривенникова В.Г., Виноградов А.Д. Митохондриальный комплекс I. Успех биол хим 2003; 43: 19-58
15. Nowak G., Clifton G.L., Bakajsova D. Succinate ameliorates energy deficits and prevents dysfunction of complex I in injured renal proximal tubular cells. J Pharmacol Exp Ther 2008; 324: 3: 1155-1162.
16. Semenza G.L., Wang G.L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 1992; 12: 5447-5454.
17. Ke Q., Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol 2006; 70: 1469-1480.
18. Semenza G. L. O2 regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF1. J Appl Physiol 2004; 96: 3: 1173-1177.
19. Koivunen P., Hirsilä M., Remes A.M. et al. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J Biol Chem 2007; 282: 7: 4524-4532.
20. Kushnir M.M., Komaromy-Hiller G., Shushan B. et al. Analysis of dicar-boxylic acids by tandem mass spectrometry. High-throughput quantitative measurement of methylmalonic acid in serum, plasma, and urine. Clin Chem 2001; 47: 11: 1993-2002.
21. Sadagopan N., Li W., Roberds S.L. et al. Circulating succinate is elevated in rodent models of hypertension and metabolic disease. Am J Hypertens 2007; 20: 1209-1215.
22. Reinke S.N., Walsh B.H., Boylan G.B. 1H NMR derived metabolom-ic profile of neonatal asphyxia in umbilical cord serum: implications for hypoxic ischemic encephalopathy. J Proteome Res 2013; 12: 9: 4230-4239.
23. Correa P.R, Kruglov E.A, Thompson M. et al. Succinate is a paracrine signal for liver damage. J Hepatol 2007; 47: 2: 262-269.
24. Hamel D., Sanchez M., Duhamel F. et al. G-protein-coupled receptor 91 and succinate are key contributors in neonatal postcerebral hypoxia-ischemia recovery. Arterioscler Thromb Vasc Biol 2014 Feb; 34: 2: 285-293.
25. Toma I., Kang J.J., Sipos A. et al. Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney. J Clin Invest 2008; 118: 2526-2534.
26. Hochachka P.W., Dressendorfer R.H. Succinate accumulation in man during exercise. European Journal of Applied Physiology and Occupational Physiology 1976; 35: 235-242.
27. Wittenberger T., Schaller H.C., Hellebrand S. An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors. J Mol Biol 2001; 307: 799-813.
28. He W., Miao F.J., Lin D.C. et al. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature 2004; 429: 6988: 188-193.
29. Peti-Peterdi J., Gevorgyan H., Lam L., Riquier-Brison A. Metabolic control of renin secretion. Pflugers Arch. 2013; 465: 1: 53-58.
30. Deen P.M., Robben J.H. Succinate receptors in the kidney. J Am Soc Nephrol 2011; 22: 8: 1416-1422.
31. Högberg C., Gidlöf O., Tan C. et al. Succinate independently stimulates full platelet activation via cAMP and phosphoinositide 3-kinase-ß signaling. J Thromb Haemost 2011; 9: 2: 361-372.
32. Hakak Y., Lehmann-Bruinsma K., Phillips S. et al. The role of the GPR91 ligand succinate in hematopoiesis. J Leukoc Biol 2009; 85: 5: 837-843.
33. Regard J.B., Sato I.T., Coughlin S.R. Anatomical profiling of G proteincoupled receptor expression. Cell 2008; 31: 135: 3: 561-571.
34. McCreath K.J., Espada S., Gâlvez B.G., Benito M., de Molina A., Sepulveda P., Cervera A.M. Targeted disruption of the SUCNR1 metabolic receptor leads to dichotomous effects on obesity. Diabetes. 2015; 64: 4: 1154-1167.
35. Zhang H., Zhang G., Gonzalez F.J. et al. Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation. PLoS Biol 2011; 9: 7: e1001112.
36. Gnana-Prakasam J.P., Ananth S., Prasad P.D. et al. Expression and irondependent regulation of succinate receptor GPR91 in retinal pigment epithelium. Invest Ophthalmol Vis Sci 2011; 52: 6: 3751-3758.
37. Li T., Hu J., Du S. et al. ERK1/2/COX-2/PGE2 signaling pathway mediates GPR91-dependent VEGF release in streptozotocin-induced diabetes. Mol Vis 2014; 31: 20: 1109-1121.
38. Favret S., Binet F., Lapalme E. et al. Deficiency in the metabolite receptor SUCNR1 (GPR91) leads to outer retinal lesions. Aging (Albany NY) 2013; 5: 6: 427-444.
39. Багненко С.Ф., Батоцыренов Б.В., Горбачев Н.Б. и др. Применение цитофлавина в коррекции метаболических нарушений у больных с разлитым перитонитом в послеоперационном периоде. Вест интенсив тер 2006; 3: 29-32
40. Ливанов Г.А., Мороз В.В., Батоцыренов Б.В., Лодягин А.Н. Пути фармакологической коррекции последствий гипоксии при критических состояниях у больных с острыми отравлениями. Анестезиол реаниматол 2003; 2: 51-54
41. Румянцева С.А., Силина Е.В., Чичановская Л.В. и др. Эффективность антиоксидантной энергокоррекции при инфаркте головного мозга (результаты многоцентрового рандомизированного исследования). Журн неврол психиатр им. С.С. Корсакова 2014; 10: 49-55
Review
For citations:
Valeev V.V., Kovalenko A.L., Talikova E.V., Zaplutanov V.A., Delvig-Kamenskaya T.Yu. Biological Functions of Succinate (a Review of Foreign Experimental Studies). Antibiot Khimioter = Antibiotics and Chemotherapy. 2015;60(9-10):33-37. (In Russ.)
Views:
644
Email this article 