Influence of lithium chloride on the apoptosis of endotheliocytes in systemic inflammatory response syndrome in patients with severe multiple injury. A retrospective study
#2020-3
PDF_2020-03_115-121 (Русский)
HTML_2020-03_115-121 (Русский)

Keywords

lithium chloride
systemic inflammatory response syndrome
apoptosis
glycogen synthase kinase 3β

How to Cite

Kuzovlev AN, Grebenchikov OA, Meshkov MA, Dolgikh VT, Prokofiev MD, Shpichko NP, Ershov AV Influence of lithium chloride on the apoptosis of endotheliocytes in systemic inflammatory response syndrome in patients with severe multiple injury. A retrospective study. Annals of Critical Care. 2020;(3):115–121. doi:10.21320/1818-474X-2020-3-115-121.

Statistic

Abstract Views: 3
PDF_2020-03_115-121 (Русский) Downloads: 0
HTML_2020-03_115-121 (Русский) Downloads: 0
Plum Analytics

Language

English Русский

Social Networks

Keywords

Up

Abstract

Objectives. The goal is to study the effect of lithium chloride on the intensity of endotheliocytes apoptosis in a monolayer in vitro under the action of blood serum of patients with the syndrome of systemic inflammatory response in severe multiple trauma.

Materials and methods. We used toxic blood serum of 5 patients with severe multiple trauma. As controls we used blood serum of 5 healthy donors. In different series of the experiment EA.hy926 endothelial cells were incubated with blood serum of a healthy person (control), with blood serum of patients with systemic inflammatory response syndrome in severe multiple trauma. Lithium chloride was added to the cell samples at final concentrations of 0.01, 0.1, 1, 10 mmol/L. After incubation the cells were removed with trypsin-versen solution fixed with 70 % ethanol and stained with propidium iodide. Cells containing fragmented genomic DNA were analyzed by flow cytometry.

Results. It was revealed that toxic serum suppressed GSK-3β phosphorylation in endotheliocytes and also caused the splitting of VE-cadherin, a decrease in the amount of claudine and actin, initiating the destruction of intercellular contacts of the endothelial monolayer and apoptosis of endotheliocytes. Incubation of a monolayer of endotheliocytes with lithium chloride at a concentration of 1.0 mmol/l and higher almost completely prevented the dismantling of claudine, actin and VE-cadherin, and also reduced the intensity of apoptosis of endotheliocytes by more than 2 times. It was found that preincubation with lithium chloride at a concentration of 1 mmol/L not only prevented the inactivation of GSK-3β, but even stimulated its phosphorylation.

Conclusion. Lithium chloride prevents the dismantling of claudine and VE-cadherin in the intercellular contacts, reduces the number of apoptotic cells in the monolayer of the endothelial cells of the EA.hy926 line under the action of the blood serum of patients with a systemic inflammatory response syndrome in severe multiple trauma, which may indicate a protective effect of the drug on endothelial barrier. The results of this investigation suggest that the protective effect of lithium chloride on endothelium is realized via GSK-3β phosphorylation.

https://doi.org/10.21320/1818-474X-2020-3-115-121
PDF_2020-03_115-121 (Русский)
HTML_2020-03_115-121 (Русский)

References

  1. Félétou M., Vanhoutte P. Endothelial dysfunction: a multifaceted disorder. Am. J. Physiol. Heart Circ. Physiol. 2006; 291(3): H985т–H1002. DOI: 10.1152/ajpheart.00292.2006
  2. Ильина Я.Ю., Фот Е.В., Кузьков В.В., Киров М.Ю. Сепсис-индуцированное повреждение эндотелиального гликокаликса (обзор литературы). Вестник интенсивной терапии им. А.И. Салтанова. 2019; 2: 32–39. DOI: 10.21320/1818-474X-2019-2-32-39 [Ilyina Y.Y., Fot E.V, Kuzkov V.V., Kirov M.Y. Sepsis-induced damage to endothelial glycocalyx (literature review). Annals of Critical Care. 2019; 2: 32–9. (In Russ)]
  3. Hirase T., Node K. Endothelial dysfunction as a cellular mechanism for vascular failure. Am. J. Physiol. Heart Circ. Physiol. 2012; 302(3): H499–H505. DOI: 10.1152/ajpheart.00325.2011
  4. Hughes C.G., Patel M.B., Pandharipande P.P. Pathophysiology of acute brain dysfunction: what’s the cause of all this confusion? Curr. Opin. Crit. Care. 2012; 18(5): 518–526. DOI: 10.1097/MCC.0b013e328357effa
  5. Opal S., van der Poll T. Endothelial barrier dysfunction in septic shock. J. Intern. Med. 2014; 277(3): 277–293. DOI: 10.1111/joim.12331
  6. Pearson T.A., Mensah G.A., Alexander R.W. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the centers for disease control and prevention and the American Heart Association. Circulation. 2003; 107(3): 499–511. DOI: 10.1161/01.CIR.0000052939.59093.45
  7. Juhaszova M., Zorov D.B, Yaniv Y., et al. Role of glycogen synthase kinase-3β in cardioprotection. Circ. Res. 2009; 104(11): 1240–1252. DOI: 10.1161/CIRCRESAHA.109.197996
  8. Мороз В.В., Силачев Д.Н., Плотников Е.Ю. и др. Механизмы повреждения и защиты клетки при ишемии/реперфузии и экспериментальное обоснование применения препаратов на основе лития в анестезиологии. Общая реаниматология. 2013; 9(1): 63. DOI: 10.15360/1813-9779-2013-1-63 [Moroz V.V., Silachev D.N., Plotnikov E.Yu., et al. Mechanisms of Cell Damage and Protection in Ischemia/Reperfusion and Experimental Rationale for the Use of Lithium-Based Preparations in Anesthesiology. General Reanimatology. 2013; 9(1): 63. (In Russ)]
  9. Острова И.В., Гребенчиков О.А., Голубева Н.В. Нейропротективное действие хлорида лития на модели остановки сердца у крыс (экспериментальное исследование). Общая реаниматология. 2019; 15(3): 73–82. DOI: 10.15360/1813-9779-2019-3-73-82 [Ostrova I.V., Grebenchikov O.A., Golubeva N.V. Neuroprotective Effect of Lithium Chloride in Rat Model of Cardiac Arrest. General Reanimatology. 2019; 15(3): 73–82. (In Russ)]
  10. Гребенчиков О.А., Лобанов А.В., Шайхутдинова Э.Р. и др. Кардиопротекторные свойства хлорида лития на модели инфаркта миокарда у крыс. Патология кровообращения и кардиохирургия. 2019; 23(2): 43–49. DOI: 10.21688/1681-3472-2019-2-43-49 [Grebenchikov O.A., Lobanov A.V., Shaikhutdinova E.R., et al. Cardioprotective properties of lithium chloride in a rat model of myocardial infarction. Circulatory pathology and cardiac surgery. 2019; 23(2): 43–49. (In Russ)]
  11. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit. Care Med. 1992; 20: 864−874.
  12. Romaschenko V.P., Zinovkin R.A., Galkin I.I., et al. Low Concentrations of Uncouplers of Oxidative Phosphorylation Prevent Inflammatory Activation of Endothelial Cells by Tumor Necrosis Factor. Biochemistry (Mosc). 2015; 80(5): 610–619. DOI: 10.1134/S0006297915050144
  13. Winn R.K., Harlan J.M. The role of endothelial cell apoptosis in inflammatory and immune diseases. J. Thrombosis and Haemostasis. 2005; 3(8): 1815–1824. DOI: 10.1111/j.1538-7836.2005.01378.x
  14. Bannerman D.D., Sathyamoorthy M., Goldblum S.E. Bacterial lipopolysaccharide disrupts endothelial monolayer integrity and survival signaling events through caspase cleavage of adherens junction proteins. J. Biol. Chem. 1998; 273: 35371–35380. DOI: 10.1074/jbc.273.52.35371
  15. Galkin I.I., Pletjushkina O.Y., Zinovkin R.A., et al. Mitochondria-targeted antioxidants prevent TNFα-induced endothelial cell damage. Biochemistry (Mosc). 2014: 79: 124–130. DOI: 10.1134/S0006297914020059
  16. Ramirez S.H., Fan S., Dykstra H., et al. Inhibition of Glycogen Synthase Kinase 3β Promotes Tight Junction Stability in Brain Endothelial Cells by Half-Life Extension of Occludin and Claudin-5. PLoS One. 2013; 8(2): e55972. DOI: 10.1371/journal.pone.0055972
  17. Plotnikov E.Y., Babenko V.A., Pevzner I.B., et al. Nephroprotective effect of GSK-3beta inhibition by lithium ions and mu-opioid receptor agonist dalargin on gentamicin-induced nephrotoxicity. Toxicology Letters J. 2013; 220: 303–308. DOI: 10.1016/j.toxlet.2013.04.023
  18. Abello P.A., Fidler S.A., Bulkley G.B., Buchman T.G. Antioxidants modulate induction of programmed endothelial cell death (apoptosis) by endotoxin. Arch. Surg. 1994; 129(2): 134–140. DOI: 10.1001/archsurg.1994.01420260030003
  19. Hoeflich K.P., Luo J., Rubie E.A., et al. Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature. 2000; 406: 86–90. DOI: 10.1038/35017574
  20. Ghosh S., Hayden M.S. New regulators of NFkappaB in inflammation. Nat. Rev. Immunol. 2008; 8: 837–848. DOI: 10.1038/nri2423
  21. Martin M., Rehani K., Jope R.S., Michalek S.M. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat. Immunol. 2005; 6: 777–784. DOI: 10.1038/ni1221
  22. Wang H.M., Zhang T., Li Q., et al. Inhibition of glycogen synthase kinase-3β by lithium chloride suppresses 6-hydroxydopamine-induced inflammatory response in primary cultured astrocytes. Neurochem. Int. 2013; 63: 345–353. DOI: 10.1016/j.neuint.2013.07.003
  23. Beurel E., Jope R.S. Glycogen synthase kinase-3 promotes the synergistic action of interferon-gamma on lipopolysaccharide-induced IL-6 production in RAW264.7 cells. Cell. Signalling. 2009; 21: 978–985. DOI: 10.1016/j.cellsig.2009.02.019
  24. Yang H.W., Hong H.L., Luo W.W., et al. mTORC2 facilitates endothelial cell senescence by suppressing Nrf2 expression via the Akt/GSK-3β/C/EBPα signaling pathway. Acta Pharmacol Sin. 2018; 39(12): 1837–1846. DOI: 10.1038/s41401-018-0079-6
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Downloads

Download data is not yet available.