S-nitrosoglutationin as an inducer of nitrosative stress and apoptosis
- Authors: Suchkova O.N.1, Abalenikhina Y.V.1, Shchulkin A.V.1, Kostyukova E.V.1, Kochanova P.D.1, Gadzhieva F.T.1, Yakusheva E.N.1, Uzbekov M.G.1
-
Affiliations:
- Ryazan State Medical University named after academician I. P. Pavlov
- Issue: Vol 27, No 9 (2024)
- Pages: 50-56
- Section: Biological chemistry
- URL: https://ogarev-online.ru/1560-9596/article/view/264824
- DOI: https://doi.org/10.29296/25877313-2024-09-07
- ID: 264824
Cite item
Abstract
Introduction. S-nitrosoglutathione is an S-nitrosylated derivative of glutathione and is considered an important mediator of the signaling effects of nitric oxide (II). In turn, nitric oxide can exhibit both regulatory and toxic effects due to the formation of active forms of nitrogen and nitrosylation of intracellular components, which can lead to the development of apoptosis. The role of nitric oxide in the regulation of apoptosis is dual, and therefore requires further study.
The aim of the work was to study the possibility of the development of nitrosative stress and apoptosis under the action of the NO donor – S-nitrosoglutathione.
Material and methods. The study was performed on a HepG2 cell culture. S-nitrosoglutathione was added to the cells at concentrations of 1, 10, 50, 100 μМ and incubated for 3 and 24 hours. Water (S-nitrosoglutathione solvent) was added to the control cells in an equivalent volume. Photometric methods were used to determine cell viability (MTT test), the concentration of nitric oxide and peroxynitrite metabolites. Expression of 3-nitrothyrosine, Bcl2 and Fas were detected by Western blot.
Results. S-nitrosoglutathione at a concentration of 100 μМ (24 h) decreased cell viability and increased concentration of peroxynitrite. The level of nitric oxide metabolites increased under the action of S-nitrosoglutathione at concentrations of 1–100 μМ and exposure periods of 3 and 24 hours, which led to an increase the expression of 3-nitrothyrosine. S-nitrosoglutathione with incubation for 3 hours and concentrations of 1–50 μM increased the level of Bcl2, at concentrations of 50–100 μM it decreased the content of Fas; when incubated for 24 hours and concentrations of 1-100 µM it decreased the level of Bcl2 and Fas.
Conclusion. Thus, in this study, it was found that S-nitrosoglutathione at concentrations of 1–50 μM and an exposure period of 3 hours has a signaling effect in HepG2 cells. S-nitrosoglutathione at a concentration of 100 μМ during incubation of 3 and 24 hours causes the development of nitrosative stress, which leads to the development of apoptosis and decreased cell viability.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
O. N. Suchkova
Ryazan State Medical University named after academician I. P. Pavlov
Author for correspondence.
Email: abalenihina88@mail.ru
ORCID iD: 0000-0001-5227-7288
Assistant, Department of Biological Chemistry
Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026Yu. V. Abalenikhina
Ryazan State Medical University named after academician I. P. Pavlov
Email: abalenihina88@mail.ru
ORCID iD: 0000-0003-0427-0967
Dr. Sc. (Med.), Associate Professor, Department of Biological Chemistry
Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026A. V. Shchulkin
Ryazan State Medical University named after academician I. P. Pavlov
Email: abalenihina88@mail.ru
ORCID iD: 0000-0003-1688-0017
Dr. Sc. (Med.), Associate Professor, Department of Pharmacology
Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026
E. V. Kostyukova
Ryazan State Medical University named after academician I. P. Pavlov
Email: abalenihina88@mail.ru
ORCID iD: 0009-0001-1596-6815
Assistant, Department of Specialized Hygienic Disciplines
Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026P. D. Kochanova
Ryazan State Medical University named after academician I. P. Pavlov
Email: abalenihina88@mail.ru
ORCID iD: 0009-0006-2189-6733
Student
Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026F. T. Gadzhieva
Ryazan State Medical University named after academician I. P. Pavlov
Email: abalenihina88@mail.ru
ORCID iD: 0009-0001-0676-0487
Student
Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026E. N. Yakusheva
Ryazan State Medical University named after academician I. P. Pavlov
Email: abalenihina88@mail.ru
ORCID iD: 0000-0001-6887-4888
Dr. Sc. (Med.), Professor, Head of the Department of Pharmacology
Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026M. G. Uzbekov
Ryazan State Medical University named after academician I. P. Pavlov
Email: uzbekovmg@gmail.com
ORCID iD: 0000-0003-3401-3339
Dr. Sc. (Med.), Professor, Head of the Brain Biochemistry Laboratory
Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026
References
- Socco S., Bovee R., Palczewski M., et al. Epigenetics: the third pillar of nitric oxide signaling. Pharmacol. Res. 2017; 121: 52–58. DOI: 10. 1016/j. phrs. 2017. 04. 011.
- Wang F., Yuan Q., Chen F., et al. Fundamental mechanisms of the cell death caused by nitrosative stress. Front Cell Dev Biol. 2021; 9: е:742483. DOI: 10. 3389/fcell. 2021. 742483.
- Wang K., Wang Y., Zhang H., et al. A Review of the Synthesis of Nitric Oxide Donor and Donor Derivatives with Pharmacological Activities. Mini Rev Med Chem. 2022; 22: 873–883. DOI: 10. 2174/1389557521666210412161801.
- Zhang C., Biggs T. D., DevarieBaez N. O. Nitrosothiols: chemistry and reactions. Chem Commun (Camb). 2017; 53: 11266–11277. DOI: 10. 1039/c7cc06574d.
- Liu Y., Weaver C. M., Sen Y., et al. The Nitric Oxide Donor, S-Nitrosoglutathione, Rescues Peroxisome Number and Activity Defects in PEX1G843D Mild Zellweger Syndrome Fibroblasts. Front Cell Dev Biol. 2021; 9: е:714710. DOI: 10. 3389/fcell. 2021. 714710.
- Zhang Y., Sun C., Xiao G. S-nitrosylation of the Peroxiredoxin-2 promotes S-nitrosoglutathionemediated lung cancer cells apoptosis via AMPK-SIRT1 pathway. Cell death and disease. 2019;10(5): 329. DOI: 10. 1038/s41419-019-1561-x.
- Kim J., Choi S., Saxena N., et al. Regulation of STAT3 and NF-κB activations by S-nitrosylation in multiplemyeloma. Free radical biology and medicine. 2017; 106: 245–253. DOI: 10. 1016/j. freeradbiomed. 2017. 02. 039.
- Щулькин А. В., Абаленихина Ю. В., Судакова Е. А. и др. Механизмы регуляции функционирования белка-транспортера Р-гликопротеина под действием оксида азота. Биохимия. 2022; 87(4): 523–538. [Shchulkin A. V., Abalenikhina Yu. V., Sudakova E. A. i dr. Mechanisms of regulation of the functioning of the P-glycoprotein transporter protein under the action of nitric oxide. Biochemistry. 2022; 87(4): 523–538 (In Russ.)]. DOI: 10. 31857/S0320972522040054.
- Mussbacher M., Stessel H., Pirker T., et al. S-nitrosoglutathione inhibits adipogenesis in 3T3-L1 preadipocytes by Snitrosation of CCAAT/enhancer-binding protein β. Sci Rep. 2019; 9(1): е:15403. DOI: 10. 1038/s41598-019-51579-x.
- Wang Y. Y., Chen M. T., Hong H. M., et al. Role of Reduced Nitric Oxide in Liver Cell Apoptosis Inhibition During Liver Damage. Arch Med Res. 2018; 49: 219–225. DOI: 10. 1016/j. arcmed. 2018. 09. 001.
- Arzumanian V. A., Kiseleva O. I., Poverennaya E. V. The Curious Case of the HepG2 Cell Line: 40 Years of Expertise. Int J Mol Sci. 2021; 4: 13135. DOI: 10. 3390/ijms222313135.
- Kumar P., Nagarajan A., Uchil P. D. Analysis of cell viability by the MTT Assay. Cold spring harb protoc. 2018; 6. DOI:10. 1101/pdb. prot095505.
- Метельская В. А., Гуманова Н. Г. Скрининг – метод определения уровня метаболитов оксида азота сыворотке человека. Клиническая лабораторная диагностика. 2005; 6: 15–18. [Metel`skaya V. A., Gumanova N. G. Skrining – metod opredeleniya urovnya metabolitov oksida azota sy`vorotke cheloveka. Klinicheskaya laboratornaya diagnostika. 2005; 6: 15–18. (In Russ.)].
- Lobysheva I. I., Serezhenkov V. A., Vanin A. F. Interaction of peroxynitrite and hydrogen peroxide with dinitrosyl iron complexes containing thiol ligands in vitro. Biochemistry. 1999; 64: 194–200.
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 7(72): 248–254.
Supplementary files
