Giselle Barreto-Torres

Publications (3)8.31 Total impact

• Article: Direct renin inhibition exerts an anti-hypertrophic effect associated with improved mitochondrial function in post-infarction heart failure in diabetic rats.

  Rebecca Parodi-Rullan, Giselle Barreto-Torres, Louis Ruiz, José Casasnovas, Sabzali Javadov
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  ABSTRACT: In addition to hypertension control, direct renin inhibition has been shown to exert direct beneficial effects on the heart in post-infarction cardiac remodeling. This study elucidates the possible contribution of mitochondria to the anti-hypertrophic effects of the direct renin inhibitor aliskiren in post-infarction heart failure complicated with diabetes in rats. Diabetes was induced in male Sprague-Dawley rats by a single injection of streptozotocin (IP, 65 mg/kg body weight). After 7 days, the animals were randomly assigned to 4 groups: sham, heart failure, sham+aliskiren, and heart failure+aliskiren. Post-infarction HF was induced by coronary artery ligation for 4 weeks. showed that heart failure reduced ejection fraction and cardiac output by 41% (P<0.01) and 42% (P<0.05), respectively, compared to sham-operated hearts. Cardiac dysfunction was associated with suppressed state 3 respiration rates and respiratory control index in mitochondria, and increased mitochondrial permeability transition pore (PTP) opening. In addition, heart failure reduced expression of the major mitochondrial sirtuin, SIRT3 and increased acetylation of cyclophilin D, a regulatory component of the PTP. Aliskiren significantly improved cardiac function and abrogated mitochondrial perturbations. Our results demonstrate that aliskiren attenuates post-infarction remodeling which is associated with its beneficial effects on mitochondria.
  Cellular Physiology and Biochemistry 01/2012; 29(5-6):841-50. · 2.86 Impact Factor
• Source

  Available from: PubMed Central

  Article: The Role of PPARα in Metformin-Induced Attenuation of Mitochondrial Dysfunction in Acute Cardiac Ischemia/Reperfusion in Rats.

  Giselle Barreto-Torres, Rebecca Parodi-Rullán, Sabzali Javadov
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  ABSTRACT: Metformin, an anti-diabetic drug, exerts cardioprotection against ischemia-reperfusion (IR) through the activation of AMPK. However, the molecular mechanisms underlying these beneficial effects remain elusive. In this study, we examined the role of PPARα in mediating cardioprotective effects of metformin on mitochondria. Hearts of male Sprague-Dawley rats perfused by Langendorff were subjected to IR in the presence or absence of metformin and the PPARβ inhibitor, GW6471. IR reduced cardiac function and compromised the structural integrity of cardiac cells evidenced by increased LDH release from the hearts. In addition, IR induced mitochondrial dysfunction as evidenced by reduced respiration and increased mitochondrial permeability transition pore (PTP) opening. However, metformin-treated hearts demonstrated improved post-ischemic recovery of cardiac function and reduced cell death that were associated with increased state 3 respiration at complexes I and II (by 27% and 32%, respectively, both p < 0.05) and decreased PTP opening (by 27%, p < 0.05) compared to untreated hearts. The protective effects of metformin on cardiac function and mitochondria were blocked by GW6471. Thus, our results demonstrate that inhibition of PPARα attenuates the beneficial effects of metformin on mitochondria in acute IR.
  International Journal of Molecular Sciences 01/2012; 13(6):7694-709. · 2.60 Impact Factor
• Article: Targeting the mitochondrial permeability transition: cardiac ischemia-reperfusion versus carcinogenesis.

  Sabzali Javadov, J Craig Hunter, Giselle Barreto-Torres, Rebecca Parodi-Rullan
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  ABSTRACT: Cardiovascular diseases and cancer continue to be major causes of death worldwide, and despite intensive research only modest progress has been reached in reducing the morbidity and mortality of these awful diseases. Mitochondria are broadly accepted as the key organelles that play a crucial role in cell life and death. They provide cells with ATP produced via oxidative phosphorylation under physiological conditions, and initiate cell death through both apoptosis and necrosis in response to severe stress. Oxidative stress accompanied by calcium overload and ATP depletion induces the mitochondrial permeability transition (mPT) with formation of pathological, non-specific mPT pores (mPTP) in the mitochondrial inner membrane. Opening of the mPTP with a high conductance results in matrix swelling ultimately inducing rupture of the mitochondrial outer membrane and releasing pro-apoptotic proteins into the cytoplasm. The ATP level is the determining factor in deciding whether cells die through apoptosis or necrosis. Cardiac cells undergoing ischemia followed by reperfusion (IR) possess exactly the same conditions mentioned above to induce mPTP opening. Due to its critical role in cell death, inhibition of mPTP opening has been accepted as a major therapeutic approach to protect the heart against IR. In contrast to cardiac IR, cancer cells exhibit less sensitivity to pore opening which can be in part explained by increased expression of mPTP compounds/modulators and metabolic remodeling. Since the main goal of chemotherapy is to provoke apoptosis, mPT induction may represent an attractive approach for the development of new cancer therapeutics to induce mitochondria-mediated cell death and prevent cell differentiation in carcinogenesis. This review focuses on the role of the mPTP in cardiac IR and cancer, and pharmacological agents to prevent or initiate mPT-mediated cell death, respectively in these diseases.
  Cellular Physiology and Biochemistry 01/2011; 27(3-4):179-90. · 2.86 Impact Factor