Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys

Abstract The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between the...

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Autores principales:	Lorena Cuenca-Bermejo, Pilar Almela, Pablo Gallo-Soljancic, José E. Yuste, Vicente de Pablos, Víctor Bautista-Hernández, Emiliano Fernández-Villalba, María-Luisa Laorden, María-Trinidad Herrero
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/def693c860d341d296c136502ae2fb58
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spelling	oai:doaj.org-article:def693c860d341d296c136502ae2fb582021-12-02T19:16:14ZCardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys10.1038/s41598-021-99237-52045-2322https://doaj.org/article/def693c860d341d296c136502ae2fb582021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99237-5https://doaj.org/toc/2045-2322Abstract The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it. We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). The dopaminergic system was significantly depleted in all MPTP-intoxicated monkeys. MPTP- and MPTP + L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP + L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP + L-DOPA-treated animals, with no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in noradrenaline (NA) metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment.Lorena Cuenca-BermejoPilar AlmelaPablo Gallo-SoljancicJosé E. YusteVicente de PablosVíctor Bautista-HernándezEmiliano Fernández-VillalbaMaría-Luisa LaordenMaría-Trinidad HerreroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lorena Cuenca-Bermejo Pilar Almela Pablo Gallo-Soljancic José E. Yuste Vicente de Pablos Víctor Bautista-Hernández Emiliano Fernández-Villalba María-Luisa Laorden María-Trinidad Herrero Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys
description	Abstract The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it. We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). The dopaminergic system was significantly depleted in all MPTP-intoxicated monkeys. MPTP- and MPTP + L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP + L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP + L-DOPA-treated animals, with no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in noradrenaline (NA) metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment.
format	article
author	Lorena Cuenca-Bermejo Pilar Almela Pablo Gallo-Soljancic José E. Yuste Vicente de Pablos Víctor Bautista-Hernández Emiliano Fernández-Villalba María-Luisa Laorden María-Trinidad Herrero
author_facet	Lorena Cuenca-Bermejo Pilar Almela Pablo Gallo-Soljancic José E. Yuste Vicente de Pablos Víctor Bautista-Hernández Emiliano Fernández-Villalba María-Luisa Laorden María-Trinidad Herrero
author_sort	Lorena Cuenca-Bermejo
title	Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys
title_short	Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys
title_full	Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys
title_fullStr	Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys
title_full_unstemmed	Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys
title_sort	cardiac tyrosine hydroxylase activation and mb-comt in dyskinetic monkeys
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/def693c860d341d296c136502ae2fb58
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Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys

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