Thioredoxin system activation is associated with the progression of experimental pulmonary arterial hypertension.

Autor: Zimmer A; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil., Teixeira RB; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil., Constantin RL; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil., Fernandes-Piedras TRG; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil., Campos-Carraro C; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil., Türck P; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil., Visioli F; Laboratory of Oral Pathology, Post-Graduation Program in Dentistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: fernanda.visioli@ufrgs.br., Baldo G; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: gbaldo@hcpa.edu.br., Schenkel PC; Laboratory of Cardiovascular Physiology, Department of Physiology and Pharmacology, Biology Institute, Universidade Federal de Pelotas (UFPel), Pelotas, Rio Grande do Sul, Brazil. Electronic address: schenkel.paulo@ufpel.edu.br., Araujo AS; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: 00029242@ufrgs.br., Belló-Klein A; Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: belklein@ufrgs.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Nov 01; Vol. 284, pp. 119917. Date of Electronic Publication: 2021 Aug 31.
DOI: 10.1016/j.lfs.2021.119917
Abstrakt: In addition to being an antioxidant, thioredoxin (Trx) is known to stimulate signaling pathways involved in cell proliferation and to inhibit apoptosis. The aim of this study was to explore the role of Trx in some of these pathways along the progression of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male rats were first divided into two groups: monocrotaline (MCT - 60 mg/kg i.p.) and control (received saline), that were further divided into three groups: 1, 2, and 3 weeks. Animals were submitted to echocardiographic analysis. Right and left ventricles were used for the measurement of hypertrophy, through morphometric and histological analysis. The lung was prepared for biochemical and molecular analysis. One week after MCT injection, there was an increase in thioredoxin reductase (TrxR) activity, a reduction in glutathione reductase (GR) activity, and an increase in Trx-1 and vitamin D3 up-regulated protein-1 (VDUP-1) expression. Two weeks after MCT injection, there was an increase in VDUP-1, Akt and cleaved caspase-3 activation, and a decrease in Trx-1 and Nrf2 expression. PAH-induced by MCT promoted a reduction in Nrf2 and Trx-1 expression as well as an increase in Akt and VDUP-1 expression after three weeks. The increase in pulmonary vascular resistance was accompanied by increased TrxR activity, suggesting an association between the Trx system and functional changes in the progression of PAH. It seems that Trx-1 activation was an adaptive response to MCT administration to cope with pulmonary remodeling and disease progression, suggesting a potential new target for PAH therapeutics.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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