Microrheological responses of erythrocytes to gasotransmitters, by inhibiting guanylate cyclase, NO synthase and blocking ATP-dependent and calcium-dependent potassium channels
A. Muravyov
, I. Tikhomirova
, E. Volkova
, A. Priezzhev
, A. Lugovtsov
, P. Mikhailov
Abstract: Background: The positive effect of gasotransmitters (GT), nitric oxide (NO) and hydrogen sulfide (H2S) on the microrheology of blood cells is known. However, the mechanisms of microrheological changes in red blood cells (RBCs) remain poorly understood. The purpose of this study was to investigate RBC microrheological responses to the action of GT donors, substrates of their endogenous synthesis and to analyze the intracellular signaling pathways associated with these processes. Methods: RBCs were separated from plasma, washed, resuspended in Ringer's solution, and aliquoted. Cells were incubated: with sodium nitroprusside (SNP, 100 M), with an H2S donor, sodium hydrosulfide (NaHS, 100 M), with an inhibitor of soluble guanylate cyclase (ODQ, 0.5 M), with ATP-dependent K blocker channels, glibenclamide (GcL, 100 M) and blocker of Ca2+-dependent K+ channels (KCa3.1) – clotrimazole (CLM, 50.0 M) The RBC deformability (RBCD) and their aggregation (RBCA) were recorded after incubation with the drugs. Results: After RBC incubation with SNP, an increase in EI by 9% was detected (p<0.01). Under these conditions, RBCA decreased by 32% (p < 0.01). An increase in EI and a decrease in RBCA were also observed after incubation of cells with NaHS, by 10 and 28%, respectively. When s-GC was inhibited with ODQ the microrheological effects of SNP and NaHS did not appear. However, blocking KATP channels did not eliminate the increase in EI and the decrease in aggregation under the influence of NaHS. While blocking KCa3.1 channels with CLM almost completely eliminated the effects of NaHS. Conclusion: Thus, the results of the study allow us to conclude that the effects of NO and H2S can be realized in red blood cells using the s-GC-cGMP signaling pathway and, perhaps through the activation of KCa3.1 channels.
Series on Biomechanics, Vol.38, No.4(2024),15-23
DOI: 10.7546/SB.03.04.2024
Keywords: aggregation; deformability; gasotransmitters; H2S; ion channels; L-arginine; L-cysteine; NO; Red blood cells
| References: (click to open/close) | [1] Baskurt, O.K. Meiselman, H.J., 2003. Blood rheology and hemodynamics Semin. Thromb. Hemost, 29, 5, 435–450. doi: 10.1055/s-2003-44551.
[2] Alexy, T., Detterich, J., Connes, P., Toth, K., Nader, E., Kenyeres, P., Arriola-Montenegro J., Ulker P., Simmonds M.J., 2022. Physical Properties of Blood and their Relationship to Clinical Conditions. Front Physiol.13, 906768. doi: 10.3389/fphys.2022.906768.
[3] Stoltz, J.F., Donner, M., Muller, S., Larcan A., 1991. Hemorheology in clinical practice. Introduction to the notion of hemorheologic profile. J Mal Vasc. 62, 61–70.
[4] Popel, A.S., Johnson, P.C., 2005. Microcirculation and Hemorheology. Annu. Rev. Fluid. Mech. 37, 43–69. doi: 10.1146/annurev.fluid.37.042604.133933.
[5] Danielczok, J.G., Terriac, E.,Hertz,L.,Petkova-Kirova,P.,Lautenschläger,F., Laschke, M.W., Kaestner, L., 2017. Red Blood Cell Passage of Small Capillaries Is Associated with Transient Ca2+-mediated Adaptations. Front Physiol. 8, 979. doi: 10.3389/fphys.2017.00979.
[6] Ugurel, E., Goksel, E., Cilek, N., Kaga, E., Yalcin, O., 2022. Proteomic Analysis of the Role of the Adenylyl Cyclase-cAMP Pathway in Red Blood Cell Mechanical Responses. Cells. 11, 7, 1250. doi: 10.3390/cells11071250.
[7] Cilek, N., Ugurel, E., Goksel E, Yalcin, O., 2024. Signaling mechanisms in red blood cells: A view through the protein phosphorylation and deformability. J Cell Physiol. 239, 3, e30958. doi: 10.1002/jcp.30958.
[8] Brunati, M., Bordin, L., Clari, G., Moret, V., 1996. The Lyn-catalyzed Tyr phosphorylation of the transmembrane band 3 protein of human erythrocytes. Eur. J. Biochem. 240, 394–399. doi.org/10.1111/j.1432-1033.1996.0394h.x
[9] Minetti, G., Ciana, A., Balduini, C., 2004. Differential sorting of tyrosine kinases and phosphotyrosine phosphatases acting on band 3 during vesiculation of human erythrocytes. Biochem. J. 377, 489–497. doi: 10.1042/BJ20031401.
[10] Saldanha, C., Silva, A.S., Gonçalves, S., Martins-Silva, J., 2007. Modulation of erythrocyte hemorheological properties by band 3 phosphorylation and dephosphorylation. Clin. Hemorheol. Microcirc. 36, 183–194.
[11] Bor-Kucukatay, M., Wenby, R.B., Meiselman, H.J., Baskurt, O.K., 2003. Effects of nitric oxide on red blood cell deformability. Am. J. Physiol. Heart Circ. Physiol. 284, 1577–1584. doi: 10.1152/ajpheart.00665.2002.
[12] Uyuklu, M., Meiselman, H.J., Baskurt, OK., 2009. Role of hemoglobin oxygenation in the modulation of red blood cell mechanical properties by nitric oxide. Nitric Oxide. 21, 1, 20-6. doi: 10.1016/j.niox.2009.03.004.
[13] Truss, N.J., Warner, T.D., 2011. Gasotransmitters and platelets. Pharmacol Ther. PharmacolTher. 132, 2, 196-203. doi: 10.1016/j.pharmthera.2011.07.001.
[14] Chen, K., Popel, A.S., 2009. Nitric oxide production pathways in erythrocytes and plasma. Biorheology. 46, 107-119. doi: 10.3233/BIR-2009-0531.
[15] Mozar, A., Connes, P., Collins, B., Hardy-Dessources, M.D., Romana, M., Lemonne, N., Bloch, W., Grau, M., 2016. Red blood cell nitric oxide synthase modulates red blood cell deformability in sickle cell anemia. Clin. Hemorheol. Microcirc. 64, 47–53. doi: 10.3233/CH-162042.
[16] Muravyov, A.V., Antonova, N., Tikhomirova, I.A., 2019. Red blood cell micromechanical responses to hydrogen sulphide and nitric oxide donors: Analysis of crosstalk of two gasotransmitters (H2S and NO). Series on Biomechanics 33(2), 34-40.
[17] Antonova, N., Khristov, K., Alexandrova, A., Muravyov, A., Velcheva, I., 2023. Development of experimental microfluidic device and methodology for assessing microrheological properties of blood. Clin. Hemorheol. Microcirc. 3, 3, 231-245. doi: 10.3233/CH-221631.
[18] Feelisch, M., Kotsonis, P., Siebe, J., Clement, B., Schmidt, H.H., 1999. The soluble guanylyl cyclase inhibitor 1H-[1,2, 4]oxadiazolo[4,3,-a] quinoxalin-1-one is a nonselective heme protein inhibitor of nitric oxide synthase and other cytochrome P-450 enzymes involved in nitric oxide donor bioactivation. Mol. Pharmacol. 56, 2. 243–253.
[19] Mustafa, A.K., Gadalla, M.M., Snyder, SH., 2009. Signalling by gasotransmitters. Sci. Signal.2, 2-8. doi: 10.1126/scisignal.268re2
[20] Grau, M., Mozar, A., Charlot, K., Lamarre ,Y., Weyel, L., Suhr, F., 2015. High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia. Br. J. Haematol. 168, 728–736. doi: 10.1111/bjh.13185
[21] Korhonen, R., Lahti, A., Kankaanranta, H., Moilanen, E., 2005. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 4,4, 471-9. doi: 10.2174/1568010054526359.
[22] Coletta, C., Papapetropoulos, A., Erdelyi, K., Olah, G., Módis, K., Panopoulos, P., Asimakopoulou, A., Gerö, D., Sharina, I., Martin, E., Szabo, C., 2012. Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci U S A. 109, 23, 9161-6. doi: 10.1073/pnas.1202916109.
[23] Bucci, M., Papapetropoulos, A., Vellecco, V., Zhou, Z., Pyriochou, A., Roussos, C., Roviezzo, F., Brancaleone, V., Cirino, G.,2010. Hydrogen sulfide is an endogenous inhibitor of phosphodiesterase activity. Arterioscler Thromb Vasc Biol. 30, 10, 1998-2004. doi: 10.1161/ATVBAHA.110.209783.
[24] Yam, M.F., Tan, C.S., Shibao, R., 2018. Vasorelaxant effect of sinensetin via the NO/sGC/cGMP pathway and potassium and calcium channels. Hypertens Res. 2018;41(10):787-797. doi: 10.1038/s41440-018-0083-8.
[25] King, A.L., Polhemus, D.J., Bhushanb, S., Otsukab, H., Kondoa, K., 2014. Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent. PNAS. 111, 3182–3187. doi: 10.1073/pnas.1321871111.
[26] King, A.L., 2018. Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology. Oxid Med Cell Longev. 6290931. doi: 10.1155/2018/6290931. eCollection 2018.
[27] Petkova-Kirova, P., Murciano, N., Iacono, G., Jansen, J., Simionato, G., Qiao, M., Van der Zwaan, C, Rotordam, M.G., John, T., Hertz, L., Hoogendijk, A.J., Becker, N., Wagner, C., Von Lindern, M., Egee, S., Van den Akker, E., Kaestner, L., 2024. The Gárdos Channel and Piezo1 Revisited: Comparison between Reticulocytes and Mature Red Blood Cells. Int J Mol Sci. 25, 3, 1416. doi: 10.3390/ijms25031416.
[28] Kaestner, L., Bogdanova., A, Egee, S., 2020. Calcium Channels and Calcium-Regulated Channels in Human Red Blood Cells. Adv Exp Med Biol. 1131, 625-648. doi: 10.1007/978-3-030-12457-1_25.
[29] Kuck, L., Peart, J.N. Simmonds, M.J., 2022. Piezo1 regulates shear-dependent nitric oxide production in human erythrocytes. Am J Physiol Heart Circ Physiol. 323, 1, H24-H37. doi: 10.1152/ajpheart.00185.2022.
[30] Rogers, S., Lew, V.L., 2021. Up-down biphasic volume response of human red blood cells to PIEZO1 activation during capillary transits. PLoS Comput Biol. 17, 3, e1008706. doi: 10.1371/journal.pcbi.1008706.
[31] Bizjak, D.A., Brinkmann, C., Bloch W., Grau, M., 2015. Increase in red blood cell-nitric oxide synthase dependent nitric oxide production during red blood cell aging in health and disease: A study on age dependent changes of rheologic and enzymatic properties in red blood cells. PLoS ONE.10, 4, e0125206. doi.org/10.1371/journal.pone.0125206
[32] Petrov, V., Lijnen, P.,1996. Regulation of human erythrocyte Na+/H+ exchange by soluble and particulate guanylate cyclase. Am J Physiol. 271, 1556-1564.
[33] Montanaro, R., Vellecco, V., Torregrossa, R., Casillo, G.M., Manzo, O.L., Mitidieri, E., Bucci, M., Castaldo, S., Sorrentino, R., Whiteman, M., Smimmo, M., Carriero, F., Terrazzano, G., Cirino, G., d'Emmanuele di Villa Bianca, R., Brancaleone, V., 2023. Hydrogen sulfide donor AP123 restores endothelial nitric oxide-dependent vascular function in hyperglycemia via a CREB-dependent pathway. Redox Biol. 62, 102657. doi: 10.1016/j.redox.2023.102657.
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| Date published: 2024-12-11
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