Abstract
Activation of the cAMP pathway by β-adrenergic stimulation and cGMP pathway by activation of guanylate cyclase substantially affects red blood cell (RBC) membrane properties in mammals. However, whether similar mechanisms are involved in RBC regulation of lower vertebrates, especially teleosts, is not elucidated yet. In this study, we evaluated the effects of adenylate cyclase activation by epinephrine and forskolin, guanylate cyclase activation by sodium nitroprusside, and the role of Na+/H+-exchanger in the changes of osmotic fragility and regulatory volume decrease (RVD) response in crucian carp RBCs. Western blot analysis of protein kinase A and protein kinase G substrate phosphorylation revealed that changes in osmotic fragility were regulated via the protein kinase A, but not protein kinase G signaling pathway. At the same time, the RVD response in crucian carp RBCs was not affected either by activation of adenylate or guanylate cyclase. Adenylate cyclase/protein kinase A activation significantly decreased RBC osmotic fragility, i.e., increased cell rigidity. Inhibition of Na+/H+-exchanger by amiloride had no effect on the epinephrine-mediated decrease of RBC osmotic fragility. NO donor SNP did not activate guanylate cyclase, however affected RBCs osmotic fragility by protein kinase G-independent mechanisms. Taken together, our data demonstrated that the cAMP/PKA signaling pathway and NO are involved in the regulation of crucian carp RBC osmotic fragility, but not in RVD response. The authors confirm that the study has no clinical trial.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Aldrich K, Saunders D, Sievert L, Sievert G (2006) Comparison of erythrocyte osmotic fragility among amphibians, reptiles, birds and mammals. Transact Kansas Acad Sci 109:149–158. https://doi.org/10.1660/0022-8443(2006)109[149:COEOFA]2.0.CO;2
Andreyeva AY, Skverchinskaya EA, Gambaryan S, Soldatov AA, Mindukshev IV (2018) Hypoxia inhibits the regulatory volume decrease in red blood cells of common frog (Rana temporaria). Comp Biochem Physiol Part Aand 219–220:44–47. https://doi.org/10.1016/j.cbpa.2018.02.016
Andreyeva AY, Soldatov AA, Krivchenko AI, Mindukshev IV, Gambaryan S (2019) Hemoglobin deoxygenation and methemoglobinemia prevent regulatory volume decrease in Crucian Carp (Carassius carassius) Red Blood Cells. Fish Physiol Biochem 45(6):1933–1940. https://doi.org/10.1007/s10695-019-00689-4
Bennett MB, Rankin JC (1985) Identification of beta-adrenergic receptors in teleost red blood cells. Comp Biochem Physiol C Comp Pharmacol Toxicol 81(2):411–414. https://doi.org/10.1016/0742-8413(85)90029-5
Berenbrink M, Koldkjaer P, Kepp O, Cossins AR (2005) Evolution of oxygen secretion in fishes and the emergence of a complex physiological system. Science 307:1752–1757. https://doi.org/10.1126/science.1107793
Borgese F, Sardet C, Cappadoro M, Pouyssegur J, Motais R (1992) Cloning and expression of a cAMP-activated Na+/H+ exchanger: evidence that the cytoplasmic domain mediates hormonal regulation. Proc Natl Acad Sci 89(15):6765–6769
Bor-Kucukatay M, Wenby RB, Meiselman HJ, Baskurt OK (2003) Effects of nitric oxide on red blood cell deformability. Am J Physiol Heart Circ Physiol 284(5):H1577–H1584. https://doi.org/10.1152/ajpheart.00665.2002
Borsakova DV, Plakhotnik ME, Koleva LD, Bovt EA, Alexandrovich YuG, Ataullakhanov FI, Sinauridze EI (2018) Comparative methodological studies of L-asparaginase encapsulation into erythrocytes. Oncohematology 13(3):91–101. https://doi.org/10.17650/1818-8346-2018-13-3-91-101. (In Russ)
Brauner CJ, Harter TS (2017) Beyond just hemoglobin: red blood cell potentiation of hemoglobin-oxygen Unloading in Fish. J Appl Physiol 123(4):935–941. https://doi.org/10.1152/japplphysiol.00114.2017
Brauner C, Wang T, Jensen F (2002) Influence of hyperosmotic shrinkage and β-adrenergic stimulation on red blood cell volume regulation and oxygen Binding Properties in Rainbow Trout and Carp. J Comp Physiol B 172(3):251–262. https://doi.org/10.1007/s00360-001-0249-5
Butt E, Abel K, Krieger M, Palm D, Hoppe V, Hoppe J, Walter U (1994) cAMP-and cGMP-dependent Protein Kinase Phosphorylation Sites of the Focal Adhesion Vasodilator-stimulated Phosphoprotein (VASP) in Vitro and in Intact Human Platelets. J Biol Chem 269(20):14509–14517
Caldwell S, Rummer JL, Brauner CJ (2006) Blood sampling techniques and storage duration: Effects on the presence and magnitude of the red blood cell beta-adrenergic response in rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol A Mol Integr Physiol 144:188–195
Cossins AR, Gibson JS (1997) Volume-sensitive transport systems and volume homeostasis in vertebrate red blood cells. J Exp Biol 200(2):343–352
Counillon L, Bouret Y, Marchiq I, Pouysségur J (2016) Na(+)/H(+) antiporter (NHE1) and lactate/H(+) symporters (MCTs) in pH homeostasis and cancer metabolism. Biochem Biophys Acta 1863(10):2465–2480. https://doi.org/10.1016/j.bbamcr.2016.02.018
de Oliveira S, Silva-Herdade AS, Saldanha C (2008) Modulation of Erythrocyte Deformability by PKC Activity. Clin Hemorheol Microcirc 39(1–4):363–373. https://doi.org/10.3233/CH-2008-1101
Dugan SG (2004) The regulation of beta-adrenoceptors in two teleost fishes. Doctoral dissertation. University of Ottawa (Canada). https://doi.org/10.20381/ruor-12769
Fange R, Holmgren S, Nilsson S (1976) Autonomic Nerve Control of the Swimbladder of the Goldsinny Wrasse Ctenolabrus Rupestris. Acta Physiol 97:292–303. https://doi.org/10.1111/j.1748-1716.1976.tb10266.x
Gambaryan S, Kobsar A, Rukoyatkina N, Herterich S, Geiger J, Smolenski A, Lohmann SM, Walter U (2010) Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex. J Biol Chem 285(24):18352–18363. https://doi.org/10.1074/jbc.M109.077602
Gamperl AK, Wilkinson M, Boutilier RG (1994) β-Adrenoreceptors in the Trout (Oncorhynchus mykiss) heart: characterization, quantification, and effects of repeated catecholamine exposure. Gen Comp Endocrinol 95(2):259–272. https://doi.org/10.1006/gcen.1994.1123
Gong L, Pitari GM, Schulz S, Waldman SA (2004) Nitric oxide signaling: systems integration of oxygen balance in defense of cell integrity. Curr Opin Hematol 11(1):7–14. https://doi.org/10.1097/00062752-200401000-00003
Gotze K, Jakobs KH (1994) Unoccupied beta-adrenoceptor-induced adenylyl cyclase stimulation in Turkey erythrocyte membranes. Eur J Pharmacol 268:151–158. https://doi.org/10.1016/0922-4106(94)90184-8
Harter TS, Zanuzzo FS, Supuran CT, Gamperl AK, Brauner CJ (2019) Functional support for a novel mechanism that enhances tissue oxygen extraction in a teleost fish. Proc Biol Sci 286(1903):20190339. https://doi.org/10.1098/rspb.2019.0339
Hirata F, Strittmatter WJ, Axelrod J (1979) beta-adrenergic receptor agonists increase phospholipid methylation, membrane fluidity, and beta-adrenergic receptor-adenylate cyclase coupling. Proc Natl Acad Sci 76(1):368–372. https://doi.org/10.1073/pnas.76.1.368
Horga JF, Gisbert J, De Agustı́n JC, Hernandez M, Zapater P (2000) A beta-2-adrenergic receptor activates adenylate cyclase in human erythrocyte membranes at physiological calcium plasma concentrations. Blood Cells Mol Dis 26(3):223–228. https://doi.org/10.1006/bcmd.2000.0299
Jennings BL, Broughton BR, Donald JA (2004) Nitric oxide control of the dorsal aorta and the intestinal vein of the Australian short-finned eel Anguilla australis. J Exp Biol 207(8):1295–1303. https://doi.org/10.1242/jeb.00883
Jensen F (1995) Regulatory volume decrease in carp red blood cells: mechanisms and oxygenation-dependency of volume-activated potassium and amino acid transport. J Exp Biol 198:155–165
Jensen FB (2004) Red Blood Cell pH, the Bohr Effect, and Other Oxygenation-linked Phenomena in Blood O2 and CO2 Transport. Acta Physiol Scandinavica 182(3):215–227. https://doi.org/10.1111/j.1365-201X.2004.01361.x
Kaloyianni M, Rasidaki A (1996) Adrenergic Responses of R. ridibunda Red Cells. J Exp Zool 276:175–185. https://doi.org/10.1002/(SICI)1097-010X(19961015)276:3%3C175::AID-JEZ1%3E3.0.CO;2-K
Koldkjaer P, Taylor E, Glass M, Wang T, Brahm J, McKenzie D, Jensen F (2002) Adrenergic Receptors, Na+/H+-exchange and Volume Regulation in Lungfish Erythrocytes. J Comp Physiol B 172(1):87–93. https://doi.org/10.1007/s00360-001-0232-1
Korbut R, Gryglewski RJ (1996) The effect of prostacyclin and nitric oxide on deformability of red blood cells in septic shock in rats. J Physiol Pharmacol 47(4):591–599
Kuwai T, Hayashi J (2006) Nitric oxide pathway activation and impaired red blood cell deformability with hypercholesterolemia. J Atheroscler Thromb 13(6):286–294. https://doi.org/10.5551/jat.13.286
Leckin T, Tuominen A, Nikinmaa M (2000) The adrenergic volume changes of immature and mature rainbow trout (Oncorhynchus mykiss) erythrocytes. J Exp Biol 203(19):3025–3031. https://doi.org/10.1242/jeb.203.19.3025
Makhro A, Huisjes R, Verhagen LP, Mañú-Pereira M, Llaudet-Planas E, Petkova-Kirova P, Wang J, Eichler H, Bogdanova A, van Wijk R, Vives-Corrons JL, Kaestner L (2016) Red cell properties after different modes of blood transportation. Front Physiol 7:288. https://doi.org/10.3389/fphys.2016.00288
Mindukshev IV, Krivoshlyk VV, Dobrylko IA, Goncharov NV, Vivulanets EV, Kuznetsov SV, Krivchenko AI (2010) Abnormalities of elastic and transporting properties of red blood cells under development of apoptosis. Biochem (Mosc) Suppl Ser A Membr Cell Biol 4(1):22–31. https://doi.org/10.1134/S1990747810010046
Mindukshev I, Kudryavtsev I, Serebriakova M, Trulioff A, Gambaryan S, Sudnitsyna J, Khmelevskoy D, Voitenko N, Avdonin P, Jenkins R, Goncharov N (2016) Flow cytometry and light scattering technique in evaluation of nutraceuticals. Neutraceuticals: Efficacy, Safety and Toxicity, 319–332. https://doi.org/10.1016/B978-0-12-802147-7.00024-3
Mindukshev IV, Krivoshlyk VV, Ermolaeva EE, Dobrylko IA, Senchenkov EV, Goncharov NV, Jenkins RO, Krivchenko AI (2007) Necrotic and apoptotic volume changes of red blood cells investigated by low-angle light scattering technique. J Spectrosc (hindawi) 21:105–120. https://doi.org/10.1155/2007/629870
Mindukshev IV, Sudnitsyna JS, Skverchinskaya EA, Andreyeva AYu, Dobrylko IA, Senchenkova EYu, Krivchenko AI, Gambaryan SP (2019) Erythrocytes’ reactions to osmotic, ammonium, and oxidative stress are inhibited under hypoxia. Biochem (Mosc) Suppl Ser A Membr Cell Biol 13(4):352–364. https://doi.org/10.1134/S1990747819040081
Motais R, Fievet B, Garcia-Romeu F, Thomas S (1989) Na+-H+ exchange and pH regulation in red blood cells: role of uncatalyzed H2CO3- dehydration. Am J Physiol 256:C728–C735. https://doi.org/10.1152/ajpcell.1989.256.4.C728
Motais R, Borgese F, Fievet B, Garcia-Romeu F (1992) Regulation of Na+/H+ Exchange and pH in Erythrocytes of Fish. Comp Biochem Physiol Comp Physiol 102(4):597–602. https://doi.org/10.1016/0300-9629(92)90710-8
Muravyov AV, Tikhomirova IA (2013) Role Molecular Signaling Pathways in Changes of Red Blood Cell Deformability. Clin Hemorheol Microcirc 53(1–2):45–59. https://doi.org/10.3233/CH-2012-1575
Muravyov AV, Koshelev VB, Fadukova OE, Tikhomirova IA, Maimistova AA, Bulaeva SV (2011) The Role of Red Blood Cell Adenylyl Cyclase Activation in Changes of Erythrocyte Membrane Microrheological Properties. Biochem (Mosc) Suppl Ser A Membr Cell Biol 5(2):128–134. https://doi.org/10.1134/S1990747811020036
Nakagawa M, Willner J, Cerri C, Reydel P (1984) The Effect of Membrane Preparation and Cellular Maturation on Human Erythrocyte AC. Biochim Biophys Acta 770:122–126. https://doi.org/10.1016/0005-2736(84)90120-2
Nikinmaa M (1982) Effects of Adrenaline on Red Cell Volume and Concentration Gradient of Protons Across the Red Cell Membrane in the Rainbow Trout, Salmo gairdneri. Mol Physiol 2:287–297
Nikinmaa M (1992) Membrane transport and control of hemoglobin-oxygen affinity in nucleated erythrocytes. Physiol Rev 72:301–321
Nikinmaa M (2012) Vertebrate red blood cells: adaptations of function to respiratory requirements, vol. 28. Springer Science & Business Media
Nikinmaa M, Huestis WH (1984) Adrenergic swelling in nucleated erythrocytes: cellular mechanisms in a bird, domestic goose, and two teleosts, striped bass and rainbow trout. J Exp Biol 113:215–224
Nikinmaa M, Jensen FB (1992) Inhibition of adrenergic proton extrusion in rainbow trout red cells by nitrite-induced methaemoglobinaemia. J Comp Physiol B 162(5):424–429. https://doi.org/10.1007/bf00258964
Olaifa F, Ayo JO, Ambali SF, Rekwot PI (2012) Effect of packaging on changes in erythrocyte osmotic fragility and malondialdehyde concentration in donkeys administered with ascorbic acid. Onderstepoort J Vet Res 79:413–418
Oonishi T, Sakashita K, Uyesaka N (1997) Regulation of red blood cell filterability by Ca2+ influx and cAMP-mediated signaling pathways. Am J Physiol 273(6):C1828–C1834. https://doi.org/10.1152/ajpcell.1997.273.6.C1828
Pafundo DE, Alvarez CL, Krumschnabel G, Schwarzbaum PJ (2010) A volume regulatory response can be triggered by nucleosides in human erythrocytes, a perfect osmometer no longer. J Biol Chem 285(9):6134–6144. https://doi.org/10.1074/jbc.M109.078246
Pedersen SF, Cala PM (2004) Comparative Biology of the Ubiquitous Na+/H+-exchanger, NHE1: Lessons From Erythrocytes. J Exp Zool A 301(7):569–578. https://doi.org/10.1002/jez.a.47
Pellegrino D, Sprovieri E, Mazza R, Randall DJ, Tota B (2002) Nitric Oxide-cGMP-mediated Vasoconstriction and Effects of Acetylcholine in the Branchial Circulation of the Eel. Comp Biochem Physiol Part A Mol Integr Physiol 132(2):447–457. https://doi.org/10.1016/S1095-6433(02)00082-X
Quiring K, Gaucher D, Kaiser G, Palm D (1973) Adenyl Cyclase Activity in Non-Nucleated Red Blood Cells: Evidence for its Localization in the Reticulocytes. Specialia: 526–527. https://doi.org/10.1007/BF01926642
Salama A, Nikinmaa M (1989) Species differences in the adrenergic responses of fish red cells: studies on whitefish, pikeperch, trout and carp. Fish Physiol Biochem 6:167–173
Salama A, Nikinmaa M (1990) Effect of Oxygen Tension on Catecholamine-induced Formation of cAMP and on Swelling of Carp Red Blood Cells. Am J Physiol Cell Physiol 259(5):C723–C726. https://doi.org/10.1152/ajpcell.1990.259.5.C723
Singh S, Ponnappan N, Verma A, Mittal A (2019) Osmotic tolerance of avian erythrocytes to complete hemolysis in solute free water. Sci Rep 9(1):7976. https://doi.org/10.1038/s41598-019-44487-7
Starzyk D, Korbut R, Gryglewski RJ (1997) The Role of Nitric Oxide in Regulation of Deformability of Red Blood Cells in Acute Phase of Endotoxaemia in Rats. J Physiol Pharmacol 48(4):731–735
Sudnitsyna JS, Skvertchinskaya EA, Dobrylko IA, Nikitina ER, Krivchenko AI, Gambaryan SP, Mindukshev IV (2016) Human erythrocyte ammonium transport is mediated by functional interaction of ammonium (RhAG) and anion (AE1) transporters. Biochem (Mosc) Suppl Ser A Membr Cell Biol 10(4):301–310. https://doi.org/10.1134/S1990747816040097
Sudnitsyna J, Skverchinskaya E, Dobrylko I, Nikitina E, Gambaryan S, Mindukshev I (2020) Microvesicle formation induced by oxidative stress in human erythrocytes. Antioxidants (Basel) 9(10):929. https://doi.org/10.3390/antiox9100929
Takakuwa Y, Ishibashi T, Mohandas N (1990) Regulation of Red Cell Membrane Deformability and Stability by Skeletal Protein Network. Biorheology 27(3–4):357–365. https://doi.org/10.3233/BIR-1990-273-412
Tuvia S, Moses A, Gulayev N, Levin S, Korenstein R (1999) b-Adrenergic Agonists Regulate Cell Membrane Fluctuations of Human Erythrocytes. J Physiol 516:781–792. https://doi.org/10.1111/j.1469-7793.1999.0781u.x
Ugur O, Onaran HO (1997) Allosteric Equilibrium Model Explains Steady-State Coupling of Beta-Adrenergic Receptors to AC in Turkey Erythrocyte Membranes. Biochem J 323:765–776. https://doi.org/10.1042/bj3230765
Walski T, Chludzińska L, Komorowska M, Witkiewicz W (2014) Individual osmotic fragility distribution: a new parameter for determination of the osmotic properties of human red blood cells. Biomed Res Int 2014:162102. https://doi.org/10.1155/2014/162102
Wood CM (1975) A Pharmacological Analysis of the Adrenergic and Cholinergic Mechanisms Regulating Branchial Vascular Resistance in the Rainbow Trout (Salmo gairdneri). Can j Zool 53:1569–1571. https://doi.org/10.1139/z75-191
Zavala K, Vandewege MW, Hoffmann FG, Opazo JC (2017) Evolution of the β-adrenoreceptors in Vertebrates. Gen Comp Endocrinol 240:129–137. https://doi.org/10.1016/j.ygcen.2016.10.005
Acknowledgements
The authors would like to thank Dr. Anna V. Kutina, Sechenov Institute of Evolutionary Physiology and Biochemistry RAS for providing the Na+/H+-exchanger inhibitor amiloride.
Funding
The study of adenylate and guanylate cyclase activation effects on the osmotic fragility and regulatory volume decrease response in crucian carp RBCs was supported by the State Assignment of Ministry of Science and Higher Education of the Russian Federation (project no. AAAA-A18-118012290371–3 to A.A.Yu., S.J.S., K.A.I., M.I.V., G.S.). The study of Na+/H+-exchanger inhibition and NO effects on the osmotic fragility of crucian carp RBCs was funded by the State Assignment (state registration number N 121041400077–1 to A.A.Yu., K.E.S.).
Author information
Authors and Affiliations
Contributions
Conceptualization: Stepan Gambaryan, Igor V. Mindukshev; Methodology: Igor V. Mindukshev; Formal analysis and investigation: Aleksandra Yu. Andreyeva; Julia S. Sudnitsyna, Ekaterina S. Kladchenko; Writing—original draft preparation: Aleksandra Yu. Andreyeva; Julia S. Sudnitsyna; Writing—review and editing: Stepan Gambaryan, Igor V. Mindukshev; Funding acquisition: Aleksander I. Krivchenko; Resources: Aleksander I. Krivchenko, Igor V. Mindukshev; Supervision: Stepan Gambaryan.
Corresponding author
Ethics declarations
Ethical approval
This study was performed in line with the principles of the Declaration of Helsinki. Approval for studies including crucian carp species was granted by the Ethics Committee of Sechenov Institute of Evolutionary Physiology and Biochemistry (Study No. 4; January 13, 2020). Studies using human platelets were approved by the Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (Study No.3–03; March 2, 2019).
Competing interests
The authors declare that they have no conflict of interest.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Andreyeva, A.Y., Kladchenko, E.S., Sudnitsyna, J.S. et al. Protein kinase A activity and NO are involved in the regulation of crucian carp (Carassius carassius) red blood cell osmotic fragility. Fish Physiol Biochem 47, 1105–1117 (2021). https://doi.org/10.1007/s10695-021-00971-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10695-021-00971-4