BECAS
DE FAZIO Rayen
congresos y reuniones científicas
Título:
Mitochondrial NHE1 and NCLX in the diabetic cardiomyopathy
Autor/es:
RAYEN DE FAZIO; FERNANDA E. CARRIZO VELASQUEZ; NOELIA COSTANTINI; SOFIA CIARROCCHI; CAROLINA JAQUENOD DE GIUSTI
Reunión:
Congreso; SCHCF + ALACF 2020 joint meeting; 2020
Resumen:
Introduction: Heart failure is the leading cause of death among diabetic people. Cellular and molecular entities leading to diabeticcardiomyopathy (DCM) are poorly understood. Na+/H+ exchanger (NHE) is a ubiquitous ion exchanger responsible for intracellularVIDEO POSTER ABSTRACTSMolecular and Cellular Physiology63pH maintenance. NHE1 is the heart isoform. Our previous results show increased NHE1 activity in the heart from obese anddiabetic mice (ob-/-) compared to the control heterozygous littermates (ob+/-). Mitochondrial dysfunction has been related tothe development of heart failure and NHE1 has been detected in rat mitochondria, where its inhibition resulted in decreasedmitochondrial swelling. Altered mitochondrial Ca2+ may result in mitochondrial dysfunction. The role of mitochondrial NHE1 andNa+/Ca2+ exchanger (NLCX) in DCM has not been yet studied. Objective to study the role of NHE1 and NLCX in the mitochondriaof ob-/- mice. Methodology: Left ventricle mitochondria were isolated by differential centrifugation. NHE1 inhibition was obtainedusing 10 µM HOE. Data were expressed as mean ± SE. Statistical analysis was performed by one-way ANOVA followed by Tukey´stest. The experimental protocol was approved by the Animal Welfare Committee of La Plata School of Medicine. Results: Ourresults showed increased NHE1 expression in the mitochondria from ob-/- mice. Preliminary results also show increased NCLXexpression. These mitochondria also presented altered swelling, mPTP opening, CRC, and ΔΨm, while NHE1 blockade partiallyreverted this phenotype. Finally, mitochondria from ob-/- mice present reduced calcium content and increased NCLX expression.Conclusions: The role of mitochondrial NHE1 is not completely understood however, NHE1 activity could not directly result inΔΨm alteration considering its electroneutral exchange. However, alterations in mitochondrial Na+ concentration could influenceNCLX activity. Considering that NHE1 inhibition partially reverses mitochondrial alterations and that our preliminary data indicatesincreased NCLX, our results indicate that both mitochondrial NHE1 and NCLX are involved in the development of mitochondrialdysfunction in DCM.