Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Significance of Catecholamine Biosynthetic/Metabolic Pathway in SARS-CoV-2 Infection and COVID-19 Severity
Δημιουργός/Συγγραφέας:	Mpekoulis, George Kalliampakou, Katerina I Milona, Raphaela S Lagou, Despoina Ioannidis, Anastasios Jahaj, Edison [EL] Χασάπης, Χρήστος[EN] Chasapis, Christos Kefallinos, Dionysis Karakasiliotis, Ioannis Kotanidou, Anastasia Chatzipanagiotou, Stylianos Vassilacopoulou, Dido Vassiliou, Alice G Angelakis, Emmanouil Vassilaki, Niki
Ημερομηνία:	2022-12-20
Γλώσσα:	Αγγλικά
ISSN:	2073-4409
DOI:	10.3390/cells12010012
Άλλο:	36611805
Περίληψη:	The SARS-CoV-2 infection was previously associated with the expression of the dopamine biosynthetic enzyme L-Dopa decarboxylase (DDC). Specifically, a negative correlation was detected between DDC mRNA and SARS-CoV-2 RNA levels in in vitro infected epithelial cells and the nasopharyngeal tissue of COVID-19 patients with mild/no symptoms. However, DDC, among other genes related to both DDC expression and SARS-CoV-2-infection (ACE2, dACE2, EPO), was upregulated in these patients, possibly attributed to an orchestrated host antiviral response. Herein, by comparing DDC expression in the nasopharyngeal swab samples of severe/critical to mild COVID-19 cases, we showed a 20 mean-fold reduction, highlighting the importance of the expression of this gene as a potential marker of COVID-19 severity. Moreover, we identified an association of SARS-CoV-2 infection with the expression of key catecholamine biosynthesis/metabolism-related genes, in whole blood samples from hospitalized patients and in cultured cells. Specifically, viral infection downregulated the biosynthetic part of the dopamine pathway (reduction in DDC expression up to 7.5 mean-fold), while enhanced the catabolizing part (increase in monoamine oxidases A and B expression up to 15 and 10 mean-fold, respectively) in vivo, irrespectively of the presence of comorbidities. In accordance, dopamine levels in the sera of severe cases were reduced (up to 3.8 mean-fold). Additionally, a moderate positive correlation between DDC and MAOA mRNA levels (r = 0.527, p < 00001) in the blood was identified upon SARS-CoV-2-infection. These observations were consistent to the gene expression data from SARS-CoV-2-infected Vero E6 and A549 epithelial cells. Furthermore, L-Dopa or dopamine treatment of infected cells attenuated the virus-derived cytopathic effect by 55% and 59%, respectively. The SARS-CoV-2 mediated suppression of dopamine biosynthesis in cell culture was, at least in part, attributed to hypoxia-like conditions triggered by viral infection. These findings suggest that L-Dopa/dopamine intake may have a preventive or therapeutic value for COVID-19 patients.
Τίτλος πηγής δημοσίευσης:	Cells
Τόμος/Κεφάλαιο:	12
Τεύχος:	1
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry [EL] Ιολογία[EN] Virology [EL] Κυτταρολογία[EN] Cytology [EL] Βιοπληροφορική[EN] Bioinformatics
Λέξεις-Κλειδιά:	L-Dopa decarboxylase SARS-CoV-2 Catecholamine pathway Disease severity Dopamine
EU Grant:	URGENCE COVID-19 NOSTOS donation
Κάτοχος πνευματικών δικαιωμάτων:	© 2022 by the authors
Όροι και προϋποθέσεις δικαιωμάτων:	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.mdpi.com/2073-4409/12/1/12
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο