Activity of Chymase, Tonin and Calpains in Rat Tissues Under Moderate Craniocerebral Hypothermia


  • Viktoriia V. Lomako Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv
  • Lyubov M. Samokhina SI L.T. Malaya National Institute of Therapy of the National Academy of Medical Sciences of Ukraine, Kharkiv



craniocerebral hypothermia, chymase, tonin, calpains, rats


The effect of moderate (32°C) craniocerebral hypothermia (CCH) on the activity of specific proteases such as chymase, tonin and calpains was studied. The proteases activity was determined in the blood serum, tissues of the central nervous system structures (cortex, hypothalamus, brain stem, cerebellum) and internal organs (heart, liver, lungs, kidneys) in animals. It has been revealed that the moderate CCH performed together with anesthesia promotes a sharp suppression of chymase and especially tonin activities (by 3-5 orders), accompanied with significant activation (in 10–50 times) of calpains. In comparison to the control the CCH led to more significant changes were found in hypothalamus, cerebellum and liver (for chymase), in the cerebellum and liver (for calpains), and if compared with the action of anesthesia the differences were present in the cerebellum, lungs, heart and kidneys (for tonin), in hypothalamus and cerebellum (for calpains).

Probl Cryobiol Cryomed 2017; 27(3): 230–241

Author Biographies

Viktoriia V. Lomako, Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv

Department of Cryophysiology

Lyubov M. Samokhina, SI L.T. Malaya National Institute of Therapy of the National Academy of Medical Sciences of Ukraine, Kharkiv



Babijchuk G.О., Samokhina L.M., Shylo O.V. et al. Chymase, tonin and calpains under hypometabolic state in rats. Probl Сryobiol 2005; 15(3): 465–466.

Bobr О.Ð., Myadelets O.D., Dubovsky V.V. Dynamics of the population of mast cells during the wound process in rats subjected to hypobiotic conditions (starvation, hypothermia). Vestnik of Vitebsk State Medical University 2006; 5(4): 21–27.

Bonaventura J., Alan D., Vejvoda J. et al. History and current use of mild therapeutic hypothermia after cardiac arrest. Arch Med Sci 2016; 12(5): 1135–1141. CrossRef PubMed

Chakraborti S., Alam M.N., Paik D. et al. Implications of calpains in health and diseases. Indian J Biochem Biophys 2012; 49(5): 316–328.

Cook C.J. Induced hypothermia in neurocritical care: A review. J Neurosci Nurs 2017; 49(1): 5–11. CrossRef PubMed

Damasceno D.D., Lima M.P., Motta D.F. et al. Cardiovascular and eletrocardiographic parameters after tonin administration in Wistar rats. Regul Pept 2013; 181(10): 30–36. CrossRef PubMed

Duffy K.R, Duffy M.S. An in situ method for the examination of calcium-dependent proteolysis. J Neurosci Methods 2011; 201(2): 333–339. CrossRef PubMed

Emirbekov E.Z., Pashaeva M.E., Aydunbekov F.T., Magomedov K.K. Influence of cerebramin and mild hypothermia on freeradical processes in rat's brain within carotid artery occlusion. Fundamental Research 2013; 10(part 4): 797–801.

Ferrario C.M. Cardiac remodelling and RAS inhibition. Ther Adv Cardiovasc Dis 2016; 10(3): 162–171. CrossRef PubMed

Goll D.E., Thompson V.F., Li H. et al. The calpain system. Physiol Rev 2003; 83(3): 731–801. CrossRef PubMed

Granic I., Nyakas C., Luiten P.G. et al. Calpain inhibition prevents amyloid-beta-induced neurodegeneration and associated behavioral dysfunction in rats. Neuropharmacol 2010; 59(4–5): 334–342.

Harvima I.T., Viinamaki H., Naukkarinen A. et al. Association of cutaneous mast cells and sensory nerves with psychic stress in psoriasis. Psychother Psychosom 1993; 60: 168–176. CrossRef PubMed

Hochachka P.W. Defense strategies against hypoxia and hypothermia. Science 1986; 231(4735): 234–241. CrossRef

Inoue K., Nishimura H., Kubota J. et al. Alternative angiotensin II formation in rats arteries occurs only at very high concentrations of angiotensin I. Hypertension 1999; 34(3): 525–530. CrossRef PubMed

Karpenko М.N., Tikhomirova M.S. The role of calpaines in the regulation of synaptic transmission. Neuroscience and Behavioral Physiology 2014; 100(4): 385–393.

Korolev V.V., Babiychyk G.A., Begunov V.G. et al., inventors. Apparatus for cooling and warming of the brain. Certificate of Authorship of the USSR â„–904695. 1982 Feb. 15.

Lesnikov D.V., Radushkevich V.L. Craniocerebral hypothermia in intensive therapy complex of metalcohol psychosis. Prikladnye Informatsyonnye Aspekty Meditsyny 2014; 17(1): 111–114.

Ley O., Bayazitoglu Y. Effect of physiology on the temperature distribution of a layered head with external convection. Int J Heat and Mass Transfer 2003; 46(17): 3233–3241. CrossRef

Lomako V.V., Samokhina L.M. Effect of rhythmic cooling on some ethological and biochemical indices in rats with experimental depression. Probl Cryobiol 2011; 21(1): 22–33.

Lomako V.V., Shylo A.V., Babijchuk G.A., Samokhina L.M. Craniocerebral hypothermia stimulates reactions of limited proteolysis in rat tissues. Probl Cryobiol Cryomed 2016; 26(3): 238–248. CrossRef

Lomonosova J.N., Shenkman B.S., Nemirovskaya T.L. Calpinedependent processes in skeletal muscles with functional discharge. Doklady Akademii Nauk 2014; 458(6): 714–717.

Lysenko L.A., Kantserova N.P., Rendakov N.L., Nemova N.N. Calpaines and their endo- and exogenous regulators at various models of neurodegeneration. Rus J Bioorganic Chem 2014; 40(6): 695–702.

Machado V.M., Morte M.I., Carreira B.P. et al. Involvement of calpains in adult neurogenesis: implications for stroke. Front Cell Neurosci 2015; 9: 22. CrossRef PubMed

Medeiros R., Kitazawa M., Chabrier M.A. et al. Calpain inhibitor A-705253 mitigates Alzheimer's disease-like pathology and cognitive decline in aged 3xTgAD mice. Am J Pathol 2012; 181(2): 616–625. CrossRef PubMed

Nurmagomedova P.M., Abasova M.M., Emirbekov E.Z. The activity of Ca2+-dependent neutral proteases in squirrel tissues in the dynamics of hibernation and during self-warming after induced awakening. Bull Exp Biol Med; 2011: 151 (5): 509–512.

Samokhina L.M. Stress, hypertension and adaptation. Enzymes of vasoconstriction and destruction at stress, hypo- and hypertension. The rhythmic cold effects. Lambert Academic Publishing, Saarbrucken; 2015.

Samokhina L.M., Dubinin A.A., inventors. A method for determining the activity of proteinases or their inhibitors in biological fluids. Patent of Ukraine â„–20171, IPC C 12 Q 1/38. 1997 Dec 25.

Samokhina L.M., Babijchuk G.О., Lomako V.V. Influence of the rhythmic cold effect on the activity of calpaines in rats with alcohol-dependent hypertension. Theoretical and practical aspects of modern cryobiology. Proc Int Correspond Sci Pract Conf; 2014 March 24; Syktyvkar, Russian; 2014: 373–382.

Samokhina L.M., Lomako V.V., Shylo O.V. Chymase, tonin and calpains under conditions of natural hibernation in hamsters. Dosyagnennya Biologii ta Medytsyny 2010; (2): 29–32.

Samokhina L.M. Lomako V.V., Shylo A.V. Influence of cold exposure on the activity of chymase and tonin in the tissues of rats. Biofizika Zhyvoy Kletki; 2014; 10: 180–182.

Samokhina L.M., Starodub N.F., Babiychuk G.A., Lomako V.V. Rhythmic cold effect on activity of elastases in female rats with alcohol-depended hypertension. Probl Cryobiol 2012; 22(1): 49–60.

Schechter N.M., Plotnick M., Selwood T. et al. Diverse effects of pH on the inhibition of human chymase by serpins. The J Biol Chem 1997; 272: 24499–24507. CrossRef PubMed

Shimizu M., Tanaka R., Uchida M. et al. Effect of Angiotensin II Type 1 receptor blocker on cardiac angiotensin-converting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters. J Vet Med Sci 2006; 68(3): 227–233. CrossRef PubMed

Shiraha H., Glading A., Chou J. et al. Activation of m-calpain (calpain II) by epidermal growth factor is limited by protein kinase A phosphorylation of m-calpain. Mol Cell Biol 2002; 22(8): 2716–2727. CrossRef PubMed

Starodub N.F., Samokhina L.M., Koval S.N., Snegurskaya I.A. Calpains: general characteristics and their role in various states of the organism. Ukr Biochem J 2014; 86(1): 5–20. CrossRef PubMed

Suzuki K., Hata S., Kawabata Y., Sorimachi H. Structure, activation, and biology of calpain. Diabetes 2004; 53(1): S12–S18.

SzczygieіJ., Mazurek J., Swiatkowski A. et al. The neuroprotective effect of mild therapeutic hypothermia after out-of-hospital cardiac arrest with successful reanimation – a case report. Pol Merkur Lekarski 2016: 40(237): 177–181.

Takai S., Jin D. Improvement of cardiovascular remodelling by chymase inhibitor. Clin Exp Pharmacol Physiol 2016; 43: 387–393. CrossRef PubMed

Takai S., Shiota N., Sakaguchi M. et al. Characterization of chymase from human vascular tissues. Clin Chim Acta 1997; 265(1): 13–20. CrossRef

Turk E.E. Hypothermia. Forensic Sci Med Pathol 2010; 6(2): 106–115. CrossRef PubMed

Wang J., Xiong W., Yang Z. et al. Human tissue kallikrein induces hypotension in transgenic mice. Hypertension 1994; 23(2): 236–243. CrossRef PubMed

Yildiz-Unal A., Korulu S., Karabay A. Neuroprotective strategies against calpain-mediated neurodegeneration. Neuropsychiatr Dis Treat 2015; 11: 297–310. CrossRef PubMed




How to Cite

Lomako, V. V., & Samokhina, L. M. (2017). Activity of Chymase, Tonin and Calpains in Rat Tissues Under Moderate Craniocerebral Hypothermia. Problems of Cryobiology and Cryomedicine, 27(3), 230–241.



Theoretical and Experimental Cryobiology