Effects of neonatal dexamethasone and CpdA on the expression of genes for apoptosis regulator proteins in the neonatal hippocampus

Авторы

  • Дмитрий Александрович Ланшаков Институт цитологии и генетики СО РАН https://orcid.org/0000-0002-8482-1302
  • Екатерина Викторовна Сухарева Институт цитологии и генетики СО РАН https://orcid.org/0000-0001-9263-9167
  • Вета Вячеславовна Булыгина Институт цитологии и генетики СО РАН
  • Тимофей Аркадьевич Лагунов Новосибирский государственный университет; Лаботатория цитометрии и биокинетики Института химической кинетики и горения
  • Татьяна Сергеевна Калинина Институт цитологии и генетики СО РАН https://orcid.org/0000-0002-2575-4621

DOI:

https://doi.org/10.33910/2687-1270-2021-2-1-41-48

Ключевые слова:

glucocorticoid receptor, brain cell type markers, development, hippocampus, neocortex, apoptosis regulator protein, proximity ligation assay (PLA)

Аннотация

Glucocorticoids (GC) are crucial regulators of homeostasis and function. Despite its negative side effects, glucocorticoid therapy in neonates is widely used antenatally for accelerating fetal lung maturation in cases of preterm birth. GC action is mediated via glucocorticoid receptors — ligand-activated transcription factors. Cell death and viability in the neonatal brain are regulated by many factors, but the glucocorticoid receptor signalling is high above them. The present work studies the changes in the expression of genes for apoptosis regulators with Bcl-2 homology (BH) domains (Bcl-xL, Bax, Bim, Bok, Bid) in the neonatal rat hippocampus after dexamethasone (DEX) and CpdA administration. CpdA is a dissociative ligand — glucocorticoid receptor modulator — that shifts glucocorticoid receptor (GR) activity toward transrepression. Ligands administration to P2 pups caused different patterns of timeline changes in the expression of the studied genes. We observed the first increase in the mRNA level of the genes which have glucocorticoid response element (GRE) (Bcl-xL, Bim) in their promoter 30 min after DEX administration. Activated GR action on cells in the neonatal hippocampus is complex and long-lasting; it could also contain receptor homo- and hetero-dimerisation. Using rat pheochromocytoma PC12 cells as a test system, we assessed GR-GR and GR-MR (mineralocorticoid receptor) dimerisation with proximity ligation assay (PLA) assay separately in the nucleus and cytoplasm after DEX and CpdA administration. An increase in GR-GR dimers in the cell nucleus was observed only after DEX administration. In the cell cytoplasm, we observed a gradual (DEX more than CpdA) increase in the number of both GR-GR and GR-MR dimers.

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Опубликован

2021-05-27

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