Abstract
Calcium is one of the most important intracellular messengers that regulate physiological and biochemical processes in the cell. Mitochondria are able to deposit calcium ions and involved in the regulation of calcium signaling. Hypothermic exposures in homeothermic animals can lead to a disruption of this important mitochondrial function and resulting pathological consequences. The aim of this study was to study the effects of moderate (30°C) hypothermia of varying duration on the calcium-accumulating ability of rat liver mitochondria. The experiments were carried out on male rats Wistar. Hypothermia was induced by external cooling of animals in a plexiglas chamber with a cold water jacket. Mitochondria were isolated from the liver of decapitated rats by differential centrifugation. The calcium-accumulating ability of mitochondria was assessed by the kinetics of calcium-induced mitochondrial swelling and their calcium retention capacity (CRC). It was found that during short-term (30-min) moderate (30°C) hypothermia, mitochondrial swelling rate decreases; hypothermia prolongation up to 1 h promotes a further decrease in the swelling rate, and up to 3 h causes its normalization. A positive correlation was found between the rate of mitochondrial calcium-induced swelling and CRC (r = 0.79). Thus, long-term cold exposure in rats activates a number of compensatory-adaptive responses. The decrease in the rate of mitochondrial calcium-induced swelling and CRC at the initial stages of hypothermia may be due to mitochondrial pore formation and is reversible.
Abbreviations
- ROS:
-
reactive oxygen species
- LPO:
-
lipid peroxidation
- P/O ratio:
-
phosphate/oxygen ratio
- MPTP:
-
mitochondrial permeability transition pore
- OPM:
-
oxidative protein modification
- VDAC:
-
voltage-dependent anion channel
- ANT:
-
adenine nucleotide translocase
- CypD:
-
cyclophilin D
- PiC:
-
mitochondrial phosphate carrier
- NADPH:
-
reduced nicotinamide adenine dinucleotide phosphate
- NAD:
-
reduced nicotinamide adenine dinucleotide
REFERENCES
Vasington FD, Murphy JV (1962) Ca ion uptake by rat kidney mitochondria and its dependence on respiration and phosphorylation, J Biol Chem 237: 2670–2677. https://doi.org/10.1016/s0021-9258(19)73805-8
Denton RM (2009) Regulation of mitochondrial dehydrogenases by calcium ions. Biochim Biophys Acta Bioenergy 1787(11): 1309–1316. https://doi.org/10.1016/j.bbabio.2009.01.005
Polderman KH (2009) Mechanisms of action, physiological effects, and compli-cations of hypothermia. Critical Care Medicine 37 (7): 186–202. https://doi.org/10.1097/CCM.0b013e3181aa5241
Sun YJ, Zhang ZY, Fan B, Li G-Y (2019) Neuroprotection by Therapeutic Hypothermia. Front Neurosci 13: 1. https://doi.org/10.3389/fnins.2019.00586
Paal P, Brugger H, Strapazzon G (2018) Accidental hypothermia. Handbook of Clinical Neurology 157: 547–563. https://doi.org/10.1016/b978-0-444-64074-1.00
Paal P, Pasquier M, Darocha T, et al. (2022) Accidental Hypothermia: 2021 Update. Int J Environ Res Public Heal 19: 501. https://doi.org/10.3390/ijerph19010501
Søreide K (2014) Clinical and translational aspects of hypothermia in major trauma patients: from pathophysiology to prevention, prognosis and potential preservation. Injury 45(4): 647–654. https://doi.org/10.1016/j.injury.2012.12.027
Hakim SM, Ammar MA, Reyad MS (2018) Effect of therapeutic hypothermia on survival and neurological outcome in adults suffering cardiac arrest: a systematic review and meta-analysis. Minerva Anestesiol 84(6): 720–730. https://doi.org/10.23736/S0375-9393.18.12164-X
Yamada KP, Kariya T, Aikawa T, Ishikawa K (2021) Effects of Therapeutic Hypothermia on Normal and Ischemic Heart. Front Cardiovasc Med 8: 1. https://doi.org/10.3389/fcvm.2021.642843
Onose G, Anghelescu A, Blendea D, Ciobanu V, Daia C, Firan FC, Oprea M, Spinu A, Popescu C, Ionescu A, Busnatu S, Munteanu С (2022) Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke. Int J Mol Sci 23: 907. https://doi.org/10.3390/ijms23020907
Klichkhanov NK, Ismailova ZG, Astaeva MD (2016) Intensity of free radical processes in rats’ blood while deep hypothermia and self-warming. Acta Biomed Sci 1(5): 104–109. https://doi.org/10.12737/23402
Alva N, Palomeque J, Carbonell T (2013) Oxidative Stress and Antioxidante Activity in Hypothermia and rewarming: can RONS Modulate the Benefical Effects of Therapeutic Hypothermia. Oxidative Med Cel Longevit 2013: 20–28. https://doi.org/10.1155/2013/957054
Schaible N, Han YS, Tveita T, Siecka GC (2018) Role of Superoxide Ion Formation in Hypothermia/Rewarming Induced Contractile Dysfunction in Cardiomyocytes. Cryobiology 81: 57–64. https://doi.org/10.1016/j.cryobiol.2018.02.010
Khalilov RA, Dzhafarova AM, Khizrieva SI, Abdullaev VR (2019) The Intensity of Free Radical Processes on Rat Liver Mitochondria under Moderate Hypothermia of Various Duration. Cell Tissue Biol 13: 446–456. https://doi.org/10.1134/S1990519X1906004X
Khizrieva SI, Khalilov RA, Dzhafarova AM, Abdullaev VR (2022) Antioxidant Status of Rat Liver Mitochondria under Conditions of Moderate Hypothermia of Different Duration. Bull Exp Biol Med 172(3): 305–309. https://doi.org/10.1007/s10517-022-05382-w
Khalilov RA, Khizrieva SI, Dzhafarova AM, Abdullaev VR (2020) The Bioenergetic characteristics of mitochondria of the rat liver at low body temperatures. Probl Biol Med Pharmaceut Chem 22(5): 35–41. https://doi.org/10.29296/25877313-2019-05-07)
Kowaltowski AJ, Castilho RF, Vercesi AE (2001) Mitochondrial permeability transition and oxidative stress. FEBS Letters 495(1–2): 12–15. https://doi.org/10.1016/S0014-5793(01)02316-X
Baranov SV, Stavrovskaya IG, Brown AM, Tyryshkin AM, Kristal BS (2008) Kinetic Model for Ca2+-induced Permeability Transition in Energized Liver Mitochondria Discriminates between Inhibitor Mechanisms. J Biol Chem 283(2): 665–676. https://doi.org/10.1074/jbc.M703484200.
Rybalchenko VK, Koganov MM (1998) Membrane structure and functions. Kiev, VSh. 312 p. (In Russ).
Lowry DH (1951) Protein measurement with the Folinphenol reagent. J Biol Chem 193(1): 265–275. https://doi.org/10.1016/s0021-9258(19)52451-6
Brookes PS, Darley-Usmar VM (2004) Role of calcium and superoxide dismutase in sensitizing mitochondria to peroxynitrite-induced permeability transition. Am J Physiol Heart Circ Physiol 286: 39–46. https://doi.org/10.1152/ajpheart.00742.2003
Marinelli F, Almagor L, Hiller R, Giladi M, Khananshvili D, Faraldo-Gómez J, Kaback HR (2014) Sodium recognition by the Na+/Ca2+ exchanger in the out ward facing conformation. Proc Natl Acad Sci USA 111: 5354–5362. https://doi.org/10.1073/pnas.1415751111
Tsai MF, Jiang D, Zhao L, Clapham D, Miller CJ (2014) Functional reconstitution of the mitochondrial Ca2+/H+ antiporter Letm1. Gen Physiol 143(1): 67–73. https://doi.org/10.1085/jgp.201311096
Belosludtsev KN, Dubinin MV, Belosludtseva NV, Mironova GD (2019) Mitochondrial Ca2+ Transport: Mechanisms, Molecular Structures, and Role in Cells. Biochemistry (Moscow). 84(6): 593–607. https://doi.org/10.1134/s0006297919060026
Petronilli V Cola C, Massari S, Colonna R, Bernardi P (1993) Physiological effectors modify voltage sensing by the cyclo-sporin A-sensitive permeability transition pore of mitochondria. J Biol Chem 268(29): 21939–21945. https://doi.org/10.1016/s0021-9258(20)80631-0
Belosludtsev KN, Belosludtseva NV, Mironova GD (2005) Possible mechanism for formation and regulation of the palmitate-induced cyclosporin A-insensitive mitochondrial pore. Biochemistry (Moscow) 70(7): 987–994. https://doi.org/10.1007/s10541-005-0189-x
Zoratti M, Szabb I (1995) The mitochondrial permeability transitions. Biochim Biophys Acta 1241(2): 139–176. https://doi.org/10.1016/0304-4157(95)00003-a
Halestrap AP (2009) What is the mitochondrial permeability transition pore? J Mol Cel Cardiol 46: 821–831. https://doi.org/10.1016/j.yjmcc.2009.02.021
Gunter TE, Yule DI, Gunter KK, Eliseev RA, Salter JD (2004) Calcium and mitochondria. FEBS Letters 567(1): 96–102. https://doi.org/10.1016/j.febslet.2004.03.071
Bernardi P, Di Lisa F (2014) The mitochondrial permeability transition pore: Molecular nature and role as a target in cardioprotection. J Mol Cel Cardiol 78:100–106. https://doi.org/10.1016/j.yjmcc.2014.09.023
Batandier СС, Leverve X, Fontaine E (2004) Opening of the Mitochondrial Permeability Transition Pore Induces Reactive Oxygen Species Production at the Level of the Respiratory Chain Complex I. J Biol Chem 279(17): 17197–17204. https://doi.org/10.1074/jbc.m310329200
McStay GP, Clarke SJ, Halestrap AP (2002) Role of critical thiol groups on the matrix surface of the adenine nucleotide translocase in the mechanism of the mitochondrial permeability transition pore. Biochem J 367:541–548. https://doi.org/10.1042/BJ20011672
Funding
This work was supported in part by the State assignment (FZNZ-2020-0002).
Author information
Authors and Affiliations
Contributions
S.I.Kh.—data collection and description; R.A.Kh.—conceptualization and experimental design; A.M.D.—statistical data processing and data interpretation; V.R.A.—critical literature analysis and conclusion generating.
Corresponding author
Ethics declarations
COMPLIANCE WITH ETHICAL STANDARDS
All applicable international, national and/or institutional principles of care and use of laboratory animals were observed. All experimental procedures that involved animals complied with ethical standards approved by legal acts of the Russian Federation, the principles of the Basel Declaration, the Order of the Russian Federation Ministry of Health no. 199n of 01.04.2016 (Rules of Good Laboratory Practice).
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest related to the publication of this article.
Additional information
Translated by A. Polyanovsky
Russian Text © The Author(s), 2023, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2023, Vol. 59, No. 4, pp. 310–318https://doi.org/10.31857/S0044452923040046,.
Rights and permissions
About this article
Cite this article
Khizrieva, S.I., Khalilov, R.A., Dzhafarova, A.M. et al. Calcium-Accumulating Ability of Rat Liver Mitochondria in Hypothermia of Various Duration. J Evol Biochem Phys 59, 1077–1085 (2023). https://doi.org/10.1134/S0022093023040063
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0022093023040063