Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats

Normotensive and hypertensive organisms respond differently to stress factors; however, the features of the central molecular genetic mechanisms underlying the reaction of the hypertensive organism to stress have not been fully established. In this study, we examined the transcriptome profiles of th...

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Main Authors: Yulia V. Makovka, Dmitry Yu. Oshchepkov, Larisa A. Fedoseeva, Arcady L. Markel, Olga E. Redina
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/13/11/1302
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author Yulia V. Makovka
Dmitry Yu. Oshchepkov
Larisa A. Fedoseeva
Arcady L. Markel
Olga E. Redina
author_facet Yulia V. Makovka
Dmitry Yu. Oshchepkov
Larisa A. Fedoseeva
Arcady L. Markel
Olga E. Redina
author_sort Yulia V. Makovka
collection DOAJ
description Normotensive and hypertensive organisms respond differently to stress factors; however, the features of the central molecular genetic mechanisms underlying the reaction of the hypertensive organism to stress have not been fully established. In this study, we examined the transcriptome profiles of the hypothalamus of hypertensive ISIAH rats, modeling a stress-sensitive form of arterial hypertension, and normotensive WAG rats at rest and after exposure to a single short-term restraint stress. It was shown that oxidative phosphorylation is the most significantly enriched process among metabolic changes in the hypothalamus of rats of both strains when exposed to a single short-term restraint stress. The analysis revealed DEGs representing both a common response to oxidative stress for both rat strains and a strain-specific response to oxidative stress for hypertensive ISIAH rats. Among the genes of the common response to oxidative stress, the most significant changes in the transcription level were observed in <i>Nos1</i>, <i>Ppargc1a</i>, <i>Abcc1</i>, <i>Srxn1</i>, <i>Cryab</i>, <i>Hspb1</i>, and <i>Fosl1</i>, among which <i>Abcc1</i> and <i>Nos1</i> are associated with hypertension, and <i>Fosl1</i> and <i>Ppargc1a</i> encode transcription factors. The response to oxidative stress specific to hypertensive rats is associated with the activation of the <i>Fos</i> gene. The DEG’s promoter region enrichment analysis allowed us to hypothesize that the response to oxidative stress may be mediated by the participation of the transcription factor CREB1 (Cyclic AMP-responsive element-binding protein 1) and the glucocorticoid receptor (NR3C1) under restraint stress in the hypothalamus of both rat strains. The results of the study revealed common and strain-specific features in the molecular mechanisms associated with oxidative phosphorylation and oxidative stress response in the hypothalamus of hypertensive ISIAH and normotensive WAG rats following a single short-term restraint stress. The obtained results expand the understanding of the most significant molecular targets for further research aimed at developing new therapeutic strategies for the prevention of the consequences of acute emotional stress, taking into account the hypertensive state of the patient.
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spelling doaj-art-b259bfcbdae04883892bd75415d200c72025-08-20T01:53:42ZengMDPI AGAntioxidants2076-39212024-10-011311130210.3390/antiox13111302Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG RatsYulia V. Makovka0Dmitry Yu. Oshchepkov1Larisa A. Fedoseeva2Arcady L. Markel3Olga E. Redina4Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, RussiaNormotensive and hypertensive organisms respond differently to stress factors; however, the features of the central molecular genetic mechanisms underlying the reaction of the hypertensive organism to stress have not been fully established. In this study, we examined the transcriptome profiles of the hypothalamus of hypertensive ISIAH rats, modeling a stress-sensitive form of arterial hypertension, and normotensive WAG rats at rest and after exposure to a single short-term restraint stress. It was shown that oxidative phosphorylation is the most significantly enriched process among metabolic changes in the hypothalamus of rats of both strains when exposed to a single short-term restraint stress. The analysis revealed DEGs representing both a common response to oxidative stress for both rat strains and a strain-specific response to oxidative stress for hypertensive ISIAH rats. Among the genes of the common response to oxidative stress, the most significant changes in the transcription level were observed in <i>Nos1</i>, <i>Ppargc1a</i>, <i>Abcc1</i>, <i>Srxn1</i>, <i>Cryab</i>, <i>Hspb1</i>, and <i>Fosl1</i>, among which <i>Abcc1</i> and <i>Nos1</i> are associated with hypertension, and <i>Fosl1</i> and <i>Ppargc1a</i> encode transcription factors. The response to oxidative stress specific to hypertensive rats is associated with the activation of the <i>Fos</i> gene. The DEG’s promoter region enrichment analysis allowed us to hypothesize that the response to oxidative stress may be mediated by the participation of the transcription factor CREB1 (Cyclic AMP-responsive element-binding protein 1) and the glucocorticoid receptor (NR3C1) under restraint stress in the hypothalamus of both rat strains. The results of the study revealed common and strain-specific features in the molecular mechanisms associated with oxidative phosphorylation and oxidative stress response in the hypothalamus of hypertensive ISIAH and normotensive WAG rats following a single short-term restraint stress. The obtained results expand the understanding of the most significant molecular targets for further research aimed at developing new therapeutic strategies for the prevention of the consequences of acute emotional stress, taking into account the hypertensive state of the patient.https://www.mdpi.com/2076-3921/13/11/1302hypothalamussingle short-term restraint stressgene expressionoxidative phosphorylationresponse to oxidative stressISIAH hypertensive rat strain
spellingShingle Yulia V. Makovka
Dmitry Yu. Oshchepkov
Larisa A. Fedoseeva
Arcady L. Markel
Olga E. Redina
Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats
Antioxidants
hypothalamus
single short-term restraint stress
gene expression
oxidative phosphorylation
response to oxidative stress
ISIAH hypertensive rat strain
title Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats
title_full Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats
title_fullStr Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats
title_full_unstemmed Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats
title_short Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats
title_sort effect of short term restraint stress on the expression of genes associated with the response to oxidative stress in the hypothalamus of hypertensive isiah and normotensive wag rats
topic hypothalamus
single short-term restraint stress
gene expression
oxidative phosphorylation
response to oxidative stress
ISIAH hypertensive rat strain
url https://www.mdpi.com/2076-3921/13/11/1302
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