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Redox-sensitive prosurvival and proapoptotic protein expression in the myocardial remodeling post-infarction in rats

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Abstract

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 (H2O2) were measured in heart tissue. The p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK-3β/GSK-3β 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 H2O2 (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-3β phosphorylation and an increase in AIF protein expression in MI group. Taken together, our results show increased H2O2 levels and cellular redox imbalance associated to a higher p-ERK and AIF immunocontent, which would contribute to a maladaptive hypertrophy phenotype.

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Acknowledgments

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Fundação de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and the Secretaria de Ciência e Tecnologia do Estado do Rio Grande do Sul (SCT-RS).

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Authors and Affiliations

  1. Physiology Department, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS, CEP 90050-170, Brazil

    Paulo Cavalheiro Schenkel, Rafael Oliveira Fernandes, Mariane Bertagnolli, Alex Sander da Rosa Araujo, Maria Flavia Marques Ribeiro & Adriane Belló-Klein

  2. Cardiovascular Research Laboratory, Clinical Hospital of Rio Grande do Sul, Porto Alegre, Brazil

    Angela Maria Vicente Tavares & Nadine Clausell

  3. Laboratory of Cellular Biology and Functional Anatomy, University of São Paulo, São Paulo, Brazil

    Gabriela Placoná Diniz & Maria Luiza Barreto-Chaves

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  1. Paulo Cavalheiro Schenkel
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  2. Angela Maria Vicente Tavares
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Correspondence to Adriane Belló-Klein.

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Schenkel, P.C., Tavares, A.M.V., Fernandes, R.O. et al. Redox-sensitive prosurvival and proapoptotic protein expression in the myocardial remodeling post-infarction in rats. Mol Cell Biochem 341, 1–8 (2010). https://doi.org/10.1007/s11010-010-0431-8

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