Mitochondria - intracellular targets of geroprotective effect of V007

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Abstract

Introduction. Oxidative stress and mitochondrial dysfunction are observed in virtually any disease associated with premature aging. Signaling molecules produced by mitochondria can act as specific targets for the action of pharmacological agents in order to regulate the processes of cellular aging, which opens up new possibilities for the search and development of drugs for effective pharmacotherapy of age-associated pathologies conditions. The aim of the study. To study the effect of V007 on the expression of mitochondrial biomarkers in rat liver cells in vivo to elucidate the possible mechanism of its geroprotective action. Methods. Molecular biological methods were used to study the expression of key mitochondrial proteins: Tom70, Tom20, VDAC, DRP1, prohibitin, Parkin, PINK1 in liver cells of young and old rats in normal conditions and with the use of the innovative drug V007. Results. The data obtained indicate that when using the V007preparation, there is a statistically significant increase in the expression of all studied mitochondrial proteins in hepatocytes of old rats to the level of young animals: DRP1 by 1.3 times; Parkin 1.2 times; PINK11.2 times; Prohibitin 1.4 times; Tom 201.3 times; Tom 701.2 times; VDAC 1.2 times. This change in the expression of mitochondrial proteins is due to the activation of their synthesis and increased activity of the mitochondrial transport systems. Conclusion. V007has a general regulatory and geroprotective effect, being a targeted pharmacological agent that regulates the functions of hepatocytes during aging by normalizing the expression of key mitochondrial proteins.

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About the authors

Igor Moiseevich Kvetnoy

Iva Pharm LLC; St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: info@spbniif.ru
Head of the Center of Molecular Biomedicine

Ekaterina Sergeevna Mironova

Iva Pharm LLC; St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Email: katerina.mironova@gerontology.ru
Senior Researcher, Center of Molecular Biomedicine

Yulia Sergeevna Krylova

St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Email: info@spbniif.ru
Senior Researcher, Center of Molecular Biomedicine

Anastasia Andreevna Mylnikova

St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Email: info@spbniif.ru
laboratory assistant researcher, Center of Molecular Biomedicine

Tatiana Stanislavovna Zubareva

St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Email: info@spbniif.ru
Senior Researcher, Center of Molecular Biomedicine

Daria Olegovna Leont’eva

St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Email: info@spbniif.ru
Research assistant, Center of Molecular Biomedicine

Victoria Olegovna Polyakova

St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Email: info@spbniif.ru
Leading Research Fellow, Center of Molecular Biomedicine

Mariya Anatolievna Petrosyan

St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation

Email: mariya@labpharm.spb.ru
Senior Researcher, Center of Molecular Biomedicine

References

  1. Jang J.Y., Blum A., Liu J., Finkel T. The role of mitochondria in aging. J. Clin. Invest. 2018; 128 (9): 3662-70. https://doi.org/10.1172/JCI120842.
  2. Son J.M., Lee C. Mitochondria: multifaceted regulators of aging. BMB Rep. 2019; 52 (1): 13-23. https://doi.org/10.5483/BM-BRep.2019.52.1.300.
  3. Rose G., Santoro A., Salvioli S. Mitochondria and mitochondria-induced signalling molecules as longevity determinants. Mech Ageing Dev. 2017; 165 (Pt B): 115-28. https://doi.org/10.10Wj.mad.2016.12.002.
  4. Wang P., Wang D., Yang Y, Hou J., Wan J., Ran F., Dai X., Zhou P., Yang Y. Tom70 protects against diabetic cardiomyopathy through its antioxidant and antiapoptotic properties. Hypertens Res. 2020; 43 (10): 1047-56. https://doi.org/10.1038/s41440-020-0518-x.
  5. Hira S., Packialakshmi B., Tang E., Zhou X. Dexamethasone upregulates mitochondrial Tom20, Tom70, and MnSOD through SGK1 in the kidney cells. J. Physiol Biochem. 2021; 77 (1): 1-11. https://doi.org/10.1007/s13105-020-00773-x.
  6. Di Maio R. , Barrett P.J., Hoffman E.K., Barrett C.W., Zharikov A., Borah A., Hu X., McCoy J., Chu Ch.T., Burton E.A., Hastings TG. , Greenamyre T. a-Synuclein binds to TOM2Ü and inhibits mitochondrial protein import in Parkinson's disease. J. Sci Transl Med. 2016; 8 (342): 342ra78. https://doi.org/10.1126/scitranslmed.aaf3634.
  7. Fang D., Maldonado E.N. VDAC Regulation: A Mitochondrial Target to Stop Cell Proliferation. Adv. Cancer Res. 2018; 138: 41-69. https://doi.org/10.1016/bs.acr.2018.02.002.
  8. Shoshan-Barmatz V, Shteinfer-Kuzmine A., Verma A. VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases. Biomolecules. 2020; 10 (11): 1485. https://doi.org/10.3390/biom10111485.
  9. Tian L., Neuber-Hess M., Mewburn J., Dasgupta A., Dunham-Snary K., Wu D. Ischemia-induced Drp1 and Fis1-mediated mitochondrial fission and right ventricular dysfunction in pulmonary hypertension. J. Mol. Med. 2017; 95: 381-93. https://doi.org/10.1007/s00109-017-1522-8.
  10. Jin J., Wei X.-X., Zhi X.-L., Wang X.-H., Meng D. Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin. 2020; 42 (5): 655-64. https://doi.org/10.1038/s41401-020-00518-y.
  11. Chowdhury D., Kumar D., Sarma P., Tangutur A., Pal Bhadra M. PHB in Cardiovascular and Other Diseases: Present Knowledge and Implications. Curr Drug Targets. 2017; 18 (16): 1836-51. https://doi.org/10.2174/1389450117666160824161225.
  12. Da Costa C.A., Duplan E., Rouland L., Checler F. The transcription factor function of Parkin: breaking the dogma. Front Neurosci. 2018; 12: 965. https://doi.org/10.3389/fnins.2018.00965.
  13. Gladkova C., Maslen S.L., Skehel J.M., Komander D. Mechanism of Parkin activation by PINK1. Nature. 2018; 559: 410-4. https://doi.org/10.1038/s41586-018-0224-x.
  14. Heo J.M., Ordureau A., Paulo J.A., Rinehart J., Harper J.W. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol. Cell. 2015; 60: 7-20. https://doi.org/10.1016/j.molcel.2015.08.016.
  15. Sekine S., Youle R.J. PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol. BMC Biol. 2018; 16 (1): 2. https://doi.org/10.1186/s12915-017-0470-7
  16. Lazarou M., Jin S.M., Kane L.A., Youle R.J. Role of PINK1 binding to the TOM complex and alternate intracellular mem branes in recruitment and activation of the E3 ligase Parkin. Dev. Cell. 2012; 22: 320-33. https://doi.org/10.10Wj.devcel.2011.12.014.
  17. Quinn P., Moreira P., Ambr6sio A., Alves C. PINK1/PARKIN signalling in neurodegeneration and neuroinflammation. Acta Neuropathol Commun. 2020; 8 (1): 189. https://doi.org/10.1186/s40478-020-01062-w.
  18. Shoshan-Barmatz V, Maldonado E.N., Krelin Y. VDAC1 at the crossroads of cell metabolism, apoptosis and cell stress. Cell Stress. 2017; 1: 11-36. https://doi.org/10.15698/cst2017.10.104.
  19. Osellame L.D. Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission. J. Cell Sci. 2016; 129: 2170-81. https://doi.org/10.1242/jcs.185165.
  20. Cooper H.A., Eguchi S. Inhibition of mitochondrial fission as a novel therapeutic strategy to reduce mortality upon myocardial infarction. Clin. Sci. 2018; 132: 2163-7. https://doi.org/10.1042/CS20180671.

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Relative area of expression of mitochondrial proteins in the liver of rats Note. * – p<0.05 compared to the group of young animals (control); ** – p<0.05 compared to the group of old animals.

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3. Fig. 2. Immunofluorescent staining with antibodies to Tom70 of liver cells of rats. A – young animals (control group), ×1000; B – old animals, ×1000; C – application of the drug V007, ×1000.

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