Registration Number
0222U001097,
0120U000020
, R & D reports
Title
Cellular and molecular mechanisms of the corrective action of vitamin D3 in neurotoxicity induced by prolonged action of glucocorticoids.
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Head
Velykiy Mykola M., Доктор біологічних наук
Registration Date
24-01-2022
Organization
Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine
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An increase in the content of 3-nitrotyrosine, poly- (ADP) -ribosylated proteins and the active subunit of p17 caspase-3 in the brain of rats with prolonged action of prednisolone was shown, which indicates the development of oxidative-nitrosative stress and increased apoptotic cell death. It has been shown that the molecular mechanisms of glucocorticoid-induced neurotoxicity are realized through increased expression (protein content) of glucocorticoid (GR) receptors and nuclear factor NF-κB, which is a potent redox-sensitive transcription factor. Simultaneously with the increase in the level of NF-κB mRNA (Nf-κb mRNA), the protein content of its transcriptionally active subunit p65 NF-κB, phosphorylated by Ser 311, increased. The efficiency of transcriptional activity of NF-κB was enhanced due to a decrease in the level of κB inhibitor (IκB), which, when combined with NF-κB, blocks its activity. The neuroprotective properties of vitamin D3 in glucocorticoid-induced neurotoxicity have been demonstrated. In particular, prolonged administration of cholecalciferol on prednisolone inhibited the development of oxidative-nitrosative stress (decreased levels of 3-nitrotyrosine, poly- (ADP) -ribosylated proteins) and the intensity of apoptotic cell death (caspase-3). In the brain's GR-NF-κB / IκB system, vitamin D3 had a partially normalizing effect on NF-κB protein and mRNA content, indicating the ability of cholecalciferol to regulate NF-κB-associated processes and reduce glucocorticoid receptor expression in holocorticoid receptors.
Product Description
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Lisakovska Olha O.
Lototska Olena Volodymyrivna
Mazanova Anna Oleksandrivna
Khalimon Tetiana V
Shimanskiy Igor O.
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2022-03-09
