Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke

Background: Cerebral ischemia, a common cerebrovascular disease, is one of the great threats to human health and new targets for stroke therapy are needed. The transcriptional activity in the cell is regulated by epigenetic processes such as DNA methylation/demethylation, acetylation/deacetylation,...

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Autores principales:	Svetlana Sharifulina, Valentina Dzreyan, Valeria Guzenko, Svetlana Demyanenko
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ischemic stroke epigenetics histone methyltransferase DNA methyltransferase Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/56d713935b8c4a00ac2aa08dd64b4fc9
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spelling	oai:doaj.org-article:56d713935b8c4a00ac2aa08dd64b4fc92021-11-25T17:57:08ZHistone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke10.3390/ijms2222124831422-00671661-6596https://doaj.org/article/56d713935b8c4a00ac2aa08dd64b4fc92021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12483https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Background: Cerebral ischemia, a common cerebrovascular disease, is one of the great threats to human health and new targets for stroke therapy are needed. The transcriptional activity in the cell is regulated by epigenetic processes such as DNA methylation/demethylation, acetylation/deacetylation, histone methylation, etc. Changes in DNA methylation after ischemia can have both neuroprotective and neurotoxic effects depending on the degree of ischemia damage, the time elapsed after injury, and the site of methylation. Methods: In this study, we investigated the changes in the expression and intracellular localization of DNA methyltransferase DNMT1, histone methyltransferases SUV39H1, and G9a in penumbra neurons and astrocytes at 4 and 24 h after stroke in the rat cerebral cortex using photothrombotic stroke (PTS) model. Methods of immunofluorescence microscopy analysis, apoptosis analysis, and immunoblotting were used. Additionally, we have studied the effect of DNMT1 and G9a inhibitors on the volume of PTS-induced infarction and apoptosis of penumbra cells in the cortex of mice after PTS. Results: This study has shown that the level of DNMT1 increased in the nuclear and cytoplasmic fractions of the penumbra tissue at 24 h after PTS. Inhibition of DNMT1 by 5-aza-2′-deoxycytidine protected cells of PTS-induced penumbra from apoptosis. An increase in the level of SUV39H1 in the penumbra was found at 24 h after PTS and G9a was overexpressed at 4 and 24 h after PTS. G9a inhibitors A-366 and BIX01294 protected penumbra cells from apoptosis and reduced the volume of PTS-induced cerebral infarction. Conclusion: Thus, the data obtained show that DNA methyltransferase DNMT1 and histone methyltransferase G9a can be potential protein targets in ischemic penumbra cells, and their inhibitors are potential neuroprotective agents capable of protecting penumbra cells from postischemic damage to the cerebral cortex.Svetlana SharifulinaValentina DzreyanValeria GuzenkoSvetlana DemyanenkoMDPI AGarticleischemic strokeepigeneticshistone methyltransferaseDNA methyltransferaseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12483, p 12483 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ischemic stroke epigenetics histone methyltransferase DNA methyltransferase Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ischemic stroke epigenetics histone methyltransferase DNA methyltransferase Biology (General) QH301-705.5 Chemistry QD1-999 Svetlana Sharifulina Valentina Dzreyan Valeria Guzenko Svetlana Demyanenko Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke
description	Background: Cerebral ischemia, a common cerebrovascular disease, is one of the great threats to human health and new targets for stroke therapy are needed. The transcriptional activity in the cell is regulated by epigenetic processes such as DNA methylation/demethylation, acetylation/deacetylation, histone methylation, etc. Changes in DNA methylation after ischemia can have both neuroprotective and neurotoxic effects depending on the degree of ischemia damage, the time elapsed after injury, and the site of methylation. Methods: In this study, we investigated the changes in the expression and intracellular localization of DNA methyltransferase DNMT1, histone methyltransferases SUV39H1, and G9a in penumbra neurons and astrocytes at 4 and 24 h after stroke in the rat cerebral cortex using photothrombotic stroke (PTS) model. Methods of immunofluorescence microscopy analysis, apoptosis analysis, and immunoblotting were used. Additionally, we have studied the effect of DNMT1 and G9a inhibitors on the volume of PTS-induced infarction and apoptosis of penumbra cells in the cortex of mice after PTS. Results: This study has shown that the level of DNMT1 increased in the nuclear and cytoplasmic fractions of the penumbra tissue at 24 h after PTS. Inhibition of DNMT1 by 5-aza-2′-deoxycytidine protected cells of PTS-induced penumbra from apoptosis. An increase in the level of SUV39H1 in the penumbra was found at 24 h after PTS and G9a was overexpressed at 4 and 24 h after PTS. G9a inhibitors A-366 and BIX01294 protected penumbra cells from apoptosis and reduced the volume of PTS-induced cerebral infarction. Conclusion: Thus, the data obtained show that DNA methyltransferase DNMT1 and histone methyltransferase G9a can be potential protein targets in ischemic penumbra cells, and their inhibitors are potential neuroprotective agents capable of protecting penumbra cells from postischemic damage to the cerebral cortex.
format	article
author	Svetlana Sharifulina Valentina Dzreyan Valeria Guzenko Svetlana Demyanenko
author_facet	Svetlana Sharifulina Valentina Dzreyan Valeria Guzenko Svetlana Demyanenko
author_sort	Svetlana Sharifulina
title	Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke
title_short	Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke
title_full	Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke
title_fullStr	Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke
title_full_unstemmed	Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke
title_sort	histone methyltransferases suv39h1 and g9a and dna methyltransferase dnmt1 in penumbra neurons and astrocytes after photothrombotic stroke
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/56d713935b8c4a00ac2aa08dd64b4fc9
work_keys_str_mv	AT svetlanasharifulina histonemethyltransferasessuv39h1andg9aanddnamethyltransferasednmt1inpenumbraneuronsandastrocytesafterphotothromboticstroke AT valentinadzreyan histonemethyltransferasessuv39h1andg9aanddnamethyltransferasednmt1inpenumbraneuronsandastrocytesafterphotothromboticstroke AT valeriaguzenko histonemethyltransferasessuv39h1andg9aanddnamethyltransferasednmt1inpenumbraneuronsandastrocytesafterphotothromboticstroke AT svetlanademyanenko histonemethyltransferasessuv39h1andg9aanddnamethyltransferasednmt1inpenumbraneuronsandastrocytesafterphotothromboticstroke
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Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke

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