Glutaredoxin-1 (Glrx) is a thioltransferase that regulates protein S-glutathiolation. To elucidate the role of endogenous Glrx in cardiovascular disease, Glrx knockout (KO) mice were infused with angiotensin II (Ang II) for 6days. After Ang II infusion, body weight and blood pressure were similar between WT and Glrx KO mice. However, compared to WT mice, Glrx KO mice demonstrated (1) less cardiac and aortic medial hypertrophy, (2) less oxidant generation in aorta as assessed by dihydroethidium staining and nitrotyrosine, (3) decreased phosphorylation of Akt in the heart, and (4) less expression of inducible NOS in aorta and heart. In cultured embryonic fibroblasts from Glrx KO mice, S-glutathiolation of actin was enhanced and actin depolymerization was impaired after hydrogen peroxide stimulation compared with WT cells. Furthermore, oxidant generation in phorbol ester-stimulated fibroblasts and RAW 264.7 macrophage-like cells was lower with Glrx siRNA knockdown. These data indicate that Ang II-induced oxidant production and hypertrophic responses were attenuated in Glrx KO mice, which may result from impaired NADPH oxidase activation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930025PMC
http://dx.doi.org/10.1016/j.freeradbiomed.2010.07.005DOI Listing

Publication Analysis

Top Keywords

glrx mice
16
oxidant generation
12
hypertrophy oxidant
8
knockout mice
8
glrx
8
mice
7
attenuated cardiovascular
4
cardiovascular hypertrophy
4
oxidant
4
generation response
4

Similar Publications

Objective: This study aimed to screen an immune-related gene (IRG) panel and develop a novel approach for diagnosing pulmonary arterial hypertension (PAH) utilizing bioinformatics and machine learning (ML).

Methods: Gene expression profiles were retrieved from the Gene Expression Omnibus (GEO) database to identify differentially expressed immune-related genes (IRG-DEGs). We employed five machine learning algorithms-LASSO, random forest (RF), boosted regression trees (BRT), XGBoost, and support vector machine recursive feature elimination (SVM-RFE) to identify biomarkers derived from IRG-DEGs associated with the diagnosis of PAH, incorporating them into the IRG-DEGs panel.

View Article and Find Full Text PDF

Developing and Verifying an Effective Diagnostic Model Linked to Immune Infiltration in Stanford Type A Aortic Dissection.

Front Biosci (Landmark Ed)

September 2024

Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China.

Background: The deadly cardiovascular condition known as Stanford type A aortic dissection (TAAD) carries a high risk of morbidity and mortality. One important step in the pathophysiology of the condition is the influx of immune cells into the aorta media, which causes medial degeneration. The purpose of this work was to investigate the potential pathogenic significance of immune cell infiltration in TAAD and to test for associated biomarkers.

View Article and Find Full Text PDF

Background And Aims: Deficiency in the thiol transferase glutaredoxin 1 (Grx1) in aging mice promotes, in a sexually dimorphic manner, dysregulation of macrophages and atherogenesis. However, the underlying mechanisms are not known. Here we tested the hypothesis that macrophage-restricted overexpression of Grx1 protects atherosclerosis-prone mice against macrophage reprogramming and dysfunction induced by a high-calorie diet (HCD) and thereby reduces the severity of atherosclerosis.

View Article and Find Full Text PDF

Objective: The feature of Parkinson's disease (PD) is the heavy dopaminergic neuron loss of substantia nigra pars compacta (SNpc), while glutaredoxin (GLRX) has been discovered to modulate the death of dopaminergic neurons. In this context, this study was implemented to uncover the impact of GRX1 on motor dysfunction and dopamine neuron degeneration in PD mice and its potential mechanism.

Methods: A PD mouse model was established via injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into mice.

View Article and Find Full Text PDF

Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome.

Arterioscler Thromb Vasc Biol

August 2023

Vascular Biology Section (E.B., S.S.P.D.L., Y.T., H.L., Y.H., Y.W., P.M.S., X.Y., J.B.G., X.W., J.H., F.S.), Department of Medicine, Boston University Chobenian & Avedisian School of Medicine, MA.

Background: Thoracic aortic aneurysms (TAAs) are abnormal aortic dilatations and a major cardiovascular complication of Marfan syndrome. We previously demonstrated a critical role for vascular smooth muscle (VSM) SirT1 (sirtuin-1), a lysine deacetylase, against maladaptive aortic remodeling associated with chronic oxidative stress and aberrant activation of MMPs (matrix metalloproteinases).

Methods: In this study, we investigated whether redox dysregulation of SirT1 contributed to the pathogenesis of TAA using fibrillin-1 hypomorphic mice (Fbn1), an established model of Marfan syndrome prone to aortic dissection/rupture.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!