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Analysis of the Role of PI3K/Akt Pathway in the Realization of the Normalizing Effect of Low-Molecular-Weight Mimetics of NGF and BDNF on Activity of Prooxidant and Antioxidant Systems in C57BL/6 Mice with Modeled Diabetes

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The effect of low-molecular-weight mimetics of NGF and BDNF (GK-2 and GSB-214 in a dose 0.5 mg/kg, respectively) on malondialdehyde content and activity of an antioxidant defense enzyme glutathione peroxidase was studied in experiments on C57BL/6 mice with streptozotocin-induced diabetes. An increase in the malondialdehyde content indicating enhanced formation of peroxidation products and a decrease of glutathione peroxidase activity in the blood plasma of untreated diabetic animals were revealed. Both studied mimetics were shown to attenuate the severity of these disorders. Since the ability of these compounds to activate the PI3K/Akt signaling pathway was previously demonstrated in vitro on HT-22 cell culture, we studied the effect of LY294002, an inhibitor of this pathway, on the above parameters. It was found that LY294002 attenuates the normalizing effect of GK-2 and GSB-214 only in relation to glutathione peroxidase activity, but not malondialdehyde level.

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References

  1. Ceriello A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care. 2003;26(5):1589-1596. doi: https://doi.org/10.2337/diacare.26.5.1589

    Article  CAS  Google Scholar 

  2. Al-Nahdi AMT, John A, Raza H. Cytoprotective Effects of N-Acetylcysteine on Streptozotocin- Induced Oxidative Stress and Apoptosis in RIN-5F Pancreatic β-Cells. Cell Physiol. Biochem. 2018;51(1):201-216. doi: https://doi.org/10.1159/000495200

    Article  CAS  Google Scholar 

  3. Ali TK, Al-Gayyar MM, Matragoon S, Pillai BA, Abdelsaid MA, Nussbaum JJ, El-Remessy AB. Diabetes-induced peroxynitrite impairs the balance of pro-nerve growth factor and nerve growth factor, and causes neurovascular injury. Diabetologia. 2011;54(3):657-668. doi: https://doi.org/10.1007/s00125-010-1935-1

    Article  CAS  Google Scholar 

  4. Pierucci D, Cicconi S, Bonini P, Ferrelli F, Pastore D, Matteucci C, Marselli L, Marchetti P, Ris F, Halban P, Oberholzer J, Federici M, Cozzolino F, Lauro R, Borboni P, Marlier LN. NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro. Diabetologia. 2001;44(10):1281-1295. doi: https://doi.org/10.1007/s001250100650

    Article  CAS  Google Scholar 

  5. Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch. Med. Sci. 2015;11(6):1164-1178. doi: https://doi.org/10.5114/aoms.2015.56342

    Article  CAS  Google Scholar 

  6. Gudasheva TA, Tarasiuk AV, Pomogaĭbo SV, Logvinov IO, Povarnina PIu, Antipova TA, Seredenin SB. Design and synthesis of dipeptide mimetics of brain-derived neurotrophic factor. Bioorg. Khim. 2012;38(3):280-290. doi: https://doi.org/10.1134/s1068162012030053

    Article  CAS  Google Scholar 

  7. Seredenin SB, Gudasheva TA. Patent US No. US9683014B2. Dipeptide Mimetics of NGF and BDNF Neurotrophins. Published June 20, 2017.

  8. Gudasheva TA, Povarnina P, Logvinov IO, Antipova TA, Seredenin SB. Mimetics of brain-derived neurotrophic factor loops 1 and 4 are active in a model of ischemic stroke in rats. Drug Des. Devel. Ther. 2016;10:3545-3553. doi: https://doi.org/10.2147/DDDT.S118768

    Article  CAS  Google Scholar 

  9. Gudasheva TA, Povarnina PY, Antipova TA, Firsova YN, Konstantinopolsky MA, Seredenin SB. Dimeric dipeptide mimetics of the nerve growth factor Loop 4 and Loop 1 activate TRKA with different patterns of intracellular signal transduction. J. Biomed. Sci. 2015;22:106. doi: https://doi.org/10.1186/s12929-015-0198-z

    Article  CAS  Google Scholar 

  10. Ostrovskaya RU, Yagubova SS, Gudasheva TA, Seredenin SB. Antidiabetic Properties of Low-Molecular-Weight BDNF Mimetics Depend on the Type of Activation of Post-Receptor Signaling Pathways. Bull. Exp. Biol. Med. 2018;164(6):734-737. doi: https://doi.org/10.1007/s10517-018-4069-y

    Article  CAS  Google Scholar 

  11. Yousif MH. Phosphoinositide 3-kinase contributes to diabetes-induced abnormal vascular reactivity in rat perfused mesenteric bed. Cell. Biochem. Funct. 2008;26(4):451-458. doi: https://doi.org/10.1002/cbf.1463

    Article  CAS  Google Scholar 

  12. Watcho P, Stavniichuk R, Tane P, Shevalye H, Maksimchyk Y, Pacher P, Obrosova IG. Evaluation of PMI-5011, an ethanolic extract of Artemisia dracunculus L., on peripheral neuropathy in streptozotocin-diabetic mice. Int. J. Mol. Med. 2011;27(3):299-307. doi: https://doi.org/10.3892/ijmm.2011.597

    Article  CAS  Google Scholar 

  13. Ostrovskaya RU, Yagubova SS, Gudasheva TA, Seredenin SB. Low-Molecular-Weight NGF Mimetic Corrects the Cognitive Deficit and Depression-like Behavior in Experimental Diabetes. Acta Naturae. 2017;9(2):94-102.

    Article  CAS  Google Scholar 

  14. Wang J, Dong Z, Lou L, Yang L, Qiu J. MiR-122 Participates in Oxidative Stress and Apoptosis in STZ-Induced Pancreatic β Cells by Regulating PI3K/AKT Signaling Pathway. Int. J. Endocrinol. 2021;2021:5525112. doi: https://doi.org/10.1155/2021/5525112

    Article  CAS  Google Scholar 

  15. Huang X, Liu G, Guo J, Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int. J. Biol. Sci. 2018;14(11): 1483-1496. doi: https://doi.org/10.7150/ijbs.27173

    Article  CAS  Google Scholar 

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Correspondence to S. S. Yagubova.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 174, No. 8, pp. 244-248, August, 2022

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Yagubova, S.S., Zolotov, N.N., Ostrovskaya, R.U. et al. Analysis of the Role of PI3K/Akt Pathway in the Realization of the Normalizing Effect of Low-Molecular-Weight Mimetics of NGF and BDNF on Activity of Prooxidant and Antioxidant Systems in C57BL/6 Mice with Modeled Diabetes. Bull Exp Biol Med 174, 273–276 (2022). https://doi.org/10.1007/s10517-023-05688-3

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  • DOI: https://doi.org/10.1007/s10517-023-05688-3

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