CHANGES OF H3 HISTONE ACETYLATION IN THE HIPPOCAMPUS OF RATS RESULTING FROM SEVERE HYPOBARIC HYPOXIA AND THE ROLE OF HYPOXIC POSTCONDITIONING

Abstract

Objective: to study the effects of severe hypobaric hypoxia (SHH) and SHH followed by moderate hypobaric hypoxia in the regime of.neuroprotective postconditioning (PostC) on H3 histone acetylation level in rat hippocampus neurons. Materials and methods: Quantitative immunohistochemical method was used for estimation of the overall histone acetylation and histone H3 acetylation by Lys9 (acH3K9) which influences the conformational properties of chromatin and gene expression in the neurons of the pyramidal layer in CA1 subfield of hippocampus in response to different modes of hypoxic exposures. Results: SHH did not cause the substantial differences in acH3K9 level at least during 4 days after exposure. PostC by mild hypobaric hypoxia significantly upregulated acH3K9 level already at Day 1 after the first episode, possibly triggering the adaptive responses caused by PostC. Conclusions: processes of histone, in particular, H3 histone acetylation, play an important role in neuroprotective effect of hypoxic PostC.

Keywords

hippocampus / severe hypoxia / hypoxic postconditioning / histone acetylation (Lys9)

References

[1] Ветровой О. В., Рыбникова Е. А., Глущенко Т. С. и др. Умеренная гипобарическая гипоксия в режиме посткондиционирования повышает экспрессию HIF-1α и эритропоэтина в СА1 поле гиппокампа крыс, переживших тяжелую гипоксию // Нейрохимия. 2014. Т. 31 (2). С. 134-139.

[2] Ветровой О. В., Рыбникова Е. А., Глущенко Т. С. И др. Влияние гипоксического посткондиционирования на экспрессию противоапоптотического белка Bcl-2 и нейротрофина BDNF в СА1 поле гиппокампа крыс, переживших тяжелую гипоксию // Морфология. 2014. Т. 145, вып. 2. С. 16-20.

[3] Самойлов М. О. Мозг и адаптация (молекулярно-клеточные механизмы). СПб.: ГНИУ Институт физиологии им. И. П. Павлова РАН, 1999. 271 с.

[4] Строев С. А., Тюлькова Е. И., Ватаева Л. А. и др. Влияние пренатальной гипоксии на экспрессию тиоредоксина-1 в гиппокампе крыс на разных сроках постнатального онтогенеза // Нейрохимия. 2011. Т. 28, № 3. С. 226-231.

[5] Baillieul S., Chacaroun S., Doutreleau S. et al. Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries? // Exp. Biol. Med. 2017. Vol. 242, № 11. P. 1198-1206.

[6] Gräff J., Kim D., Dobbin M. M., Tsai L. H. Epigenetic regulation of gene expression in physiological and pathological brain processes // Physiol. Rev. 2011. Vol. 91. P. 603-649.

[7] Johnson A. B., Barton M. C. Hypoxia-induced and stress-specifiс changes in chromatin structure and function // Mutat. Res. 2007. Vol. 618, № 1-2. P. 149-162.

[8] Melvin A., Rocha S. Chromatin as an oxygen sensor and active player in the hypoxia response // Cell Signal. 2012. Vol. 24, № 1. P. 35-43.

[9] Perez-Perri J. I., Acevedo J. M., Wappner P. Epigenetics: new questions on the response to hypoxia // Int. J. Mol. Sci. 2011. Vol. 12. P. 4705-4721.

[10] Samoilov M., Churilova A., Gluschenko T. et al. Acetylation of histones in neocortex and hippocampus of rats exposed to different modes of hypobaric hypoxia: implications for brain hypoxic injury and tolerance // Acta Histochemica. 2016. Vol. 118, № 2. P. 80-89.

[11] Schweizer S., Meisel A., Marschenz S. Epigenetic mechanisms in cerebral ischemia // J. Cereb. Blood Flow Metab. 2013. Vol. 38. P. 1335-1346.

[12] Stankiewicz A. M., Swiergiel A. H., Lisowski P. Epigenetics of stress adaptations in the brain // Brain Res. Bull. 2013. Vol. 98. P. 76-92.

[13] Vetrovoy O., Tulkova E., Sarieva K. et al. Neuroprotective effect of hypobaric hypoxic postconditioning is accompanied by dna protection and lipid peroxidation changes in rat hippocampus // Neurosci. Lett. 2017. Vol. 639. P. 49-52.

RIGHTS & PERMISSIONS

Eco-Vector