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Insulin Increases Viability of Neurons in Rat Cerebral Cortex and Normalizes Bax/Bcl-2 Ratio under Conditions of Oxidative Stress

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We studied the protective effect of insulin in various concentrations and its effect on the Bax/ Bcl-2 ratio in neurons of rat cerebral cortex under conditions of oxidative stress. The protective effect of insulin was dose-dependent within the nanomolar range (1 nM<10 nM<100 nM). Preincubation with insulin in concentrations of 100 nM and 1 μM significantly increased Bcl-2 content in neurons in 5, 30, and 45 min and 1, 2, and 4 h after the start of cell exposure to H2O2. This prooxidant increased the Bax/Bcl-2 ratio in neurons to 141-164% in comparison with the control (100%); preincubation of neurons with insulin returned this ratio to normal.

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References

  1. Sukhov IB, Shipilov VN, Chistyakova OV, Trost AM, Shpakov AO. Long-term intranasal insulin administration improves spatial memory in male rats with prolonged type 1 diabetes mellitus and in healthy rats. Doklady Biol. Sci. 2013;453(1):349-352.

    Article  CAS  Google Scholar 

  2. Cheng Y, Loh YP, Birch NP. Neuroserpin attenuates H2O2-induced oxidative stress in hippocampal neurons via AKT and BCL-2 signaling pathways. J. Mol. Neurosci. 2017;61(1):123-131.

    Article  PubMed  CAS  Google Scholar 

  3. Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer’s disease dementia. J. Alzheimers Dis. 2015;44(3):897-906.

    Article  PubMed  CAS  Google Scholar 

  4. Duarte AI, Santos MS, Oliveira CR, Rego AC. Insulin neuroprotection against oxidative stress in cortical neurons — involvement of uric acid and glutathione antioxidant defenses. Free Radic. Biol. Med. 2005;39(7):876-889.

    Article  PubMed  CAS  Google Scholar 

  5. Duarte AI, Santos P, Oliveira CR, Santos MS, Rego AC. Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signaling pathways and changes in protein expression. Biochim. Biophys. Acta. 2008;1783(6):994-1002.

    Article  PubMed  CAS  Google Scholar 

  6. Kim B, Sullivan KA, Backus C, Feldman EL. Cortical neurons develop insulin resistance and blunted Akt signaling: a potential mechanism contributing to enhanced ischemic injury indiabetes. Antioxid. Redox Sign. 2011;14(10):1829-1839.

    Article  CAS  Google Scholar 

  7. Pugazhenthi S, Miller E, Sable C, Young P, Heidenreich KA, Boxer LM, Reusch JE. Insulin-like growth factor-I induces bcl-2 promoter through the transcription factor cAMP-response element-binding protein. J. Biol. Chem. 1999;274(39):27 529-27 535.

    Article  CAS  Google Scholar 

  8. Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE, Reusch JE. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J. Biol. Chem. 2000;275(15):10,761-10,766.

    Article  CAS  Google Scholar 

  9. Shah AK, Gupta A, Dey CS. AICAR induced AMPK activation potentiates neuronal insulin signaling and glucose uptake. Arch. Biochem. Biophys. 2011;509(2):142-146.

    Article  PubMed  CAS  Google Scholar 

  10. Shpakov AO, Derkach KV, Berstein LM. Brain signaling systems in the Type 2 diabetes and metabolic syndrome: promising target to treat and prevent these diseases. Future Sci. OA. 2015;1(3):FSO25. doi: https://doi.org/10.4155/fso.15.23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Sieuwerts AM, Klijn JG, Peters HA, Foekens JA. The MTT tetrazolium salt assay scrutinized: how to use this assay reliably to measure metabolic activity of cell cultures in vitro for the assessment of growth characteristics, IC50-values and cell survival. Eur. J. Clin. Chem. Clin. Biochem. 1995;33(11):813-823.

    PubMed  CAS  Google Scholar 

  12. Zakharova IO, Sokolova TV, Avrova NF. Alpha-tocopherol prevents a dramatic oxidative stress-induced decline of the BCL-2 concentration in cortical neurons. Neurochem. J. 2016;10(3):226-231.

    Article  CAS  Google Scholar 

  13. Zakharova IO, Sokolova TV, Vlasova YA, Bayunova LV, Rychkova MP, Avrova NF. α-Tocopherol at nanomolar concentration protects cortical neurons against oxidative stress. Int. J. Mol. Sci. 2017;18(1). pii: E216. doi: https://doi.org/10.3390/ijms18010216.

  14. Zhang L, Zhao H, Zhang X, Chen L, Zhao X, Bai X, Zhang J. Nobiletin protects against cerebral ischemia via activating the p-Akt, p-CREB, BDNF and Bcl-2 pathway and ameliorating BBB permeability in rat. Brain Res. Bull. 2013;96:45-53.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Molecular Endocrinology and Neurochemistry, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, St. Petersburg, Russia

    L. V. Bayunova, I. I. Zorina, I. O. Zakharova & N. F. Avrova

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  1. L. V. Bayunova
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  2. I. I. Zorina
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  3. I. O. Zakharova
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  4. N. F. Avrova
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Correspondence to N. F. Avrova.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 165, No. 1, pp. 20-24, January, 2018

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Bayunova, L.V., Zorina, I.I., Zakharova, I.O. et al. Insulin Increases Viability of Neurons in Rat Cerebral Cortex and Normalizes Bax/Bcl-2 Ratio under Conditions of Oxidative Stress. Bull Exp Biol Med 165, 14–17 (2018). https://doi.org/10.1007/s10517-018-4088-8

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  • DOI: https://doi.org/10.1007/s10517-018-4088-8

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