Redox-sensitive prosurvival and proapoptotic protein expression in the myocardial remodeling post-infarction in rats.
In this study, we investigated the oxidative stress influence in some prosurvival and proapoptotic proteins after myocardial infarction (MI). Male Wistar rats were divided in two groups: Sham-operated (control) and MI. MI was induced by left coronary artery occlusion. 28-days after surgery, echocardiographic, morphometric, and hemodynamic parameters were evaluated. Redox status (reduced to oxidized glutathione ratio, GSH/GSSG) and hydrogen peroxide levels (H(2)O(2)) were measured in heart tissue. The p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK-3beta/GSK-3beta ratios, as well as apoptosis-inducing factor (AIF) myocardial protein expression were quantified by Western blot. MI group showed an increase in cardiac hypertrophy (23%) associated with a decrease in ejection fraction (38%) and increase in left ventricular end-diastolic pressure (82%) when compared to control, characterizing ventricular dysfunction. Redox status imbalance was seen in MI animals, as evidenced by the decrease in the GSH/GSSG ratio (30%) and increased levels of H(2)O(2) (45%). This group also showed an increase in the ERK phosphorylation and a reduction of Akt and mTOR phosphorylation when compared to control. Moreover, we showed a reduction in the GSK-3beta phosphorylation and an increase in AIF protein expression in MI group. Taken together, our results show increased H(2)O(2) levels and cellular redox imbalance associated to a higher p-ERK and AIF immunocontent, which would contribute to a maladaptive hypertrophy phenotype.
Schenkel
Paulo Cavalheiro
PC
Physiology Department, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 Porto Alegre, RS CEP 90050-170, Brazil.
Tavares
Angela Maria Vicente
AM
Fernandes
Rafael Oliveira
RO
Diniz
Gabriela Placoná
GP
Bertagnolli
Mariane
M
da Rosa Araujo
Alex Sander
AS
Barreto-Chaves
Maria Luiza
ML
Ribeiro
Maria Flavia Marques
MF
Clausell
Nadine
N
Belló-Klein
Adriane
A
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000032:analysis*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis*; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D006861:Hydrogen Peroxide / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000502:physiology*
D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; D005978:Glutathione