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Garcia-Rivas 2013 Abstract MiP2013

From Bioblast
Garcia-Rivas G,Morales JA, Vega-Sevilla L, Silva-Platas C, García N (2013) Regulation of mitochondrial permeability transition by Sirt3-catalyzed cyclophilin D deacetylation and its relevance for ventricular dysfunction in metabolic syndrome. Mitochondr Physiol Network 18.08.

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Gerardo Garcia-Rivas

MiP2013, Book of Abstracts Open Access

Garcia-Rivas G, Morales JA, Vega-Sevilla L, Silva-Platas C, Garcia N (2013)

Event: MiPNet18.08_MiP2013

Metabolic syndrome (MS) can be defined as a group of signs that increases the risk of cardiovascular diseases (CVD). These signs include central obesity, hypertriglyceridemia and hypertension. We are interested in the mechanisms that trigger ventricular dysfunction in a MS murine model, as a way to understand how mitochondrial function fails in CVD. The sustained opening of the mitochondrial permeability transition pore (PTP) is a major event in the onset of irreversible myocardial injury. Several mitochondrial proteins modulate the PTP, including the cyclophilin D (CyD), the adenine nucleotide translocator (ANT) and the SIRTUINS. In this regard, SIRT-3 has emerged recently as a pivotal mediator of mitochondrial metabolism and PTP inductor in a knockout murine model. However, the precise role of SIRT-•3 in a pathophysiologic context remains indefinable. Male Wistar rats with sucrose-induced MS were subjected to cardiac echocardiography and ex-vivo contraction measurements at 6 and 12 months. Respiratory activity, calcium retention capacity and deacetylation profile were investigated in isolated mitochondria. The expression of SIRT-3, ANT and CyD was evaluated by qPCR or western blot. We observed differences in the E/A ratio (control 1.07±0.01 vs. MS 0.85±0.06, P<0.029) and the ventricular deceleration time (0.029±0.002 vs. 0.034±0.003, P<0.04) indicating an abnormal lusitropism. No significant differences were found in respiratory activity and respiratory control from isolated mitochondria. Nevertheless, calcium retention in MS mitochondria was reduced (0.83±0.03 vs 0.65±0.04 Abs.min-1, P<0.004) indicating premature PTP opening. Proneness in PTP opening was associated with lower expression (60% p<0.001) of SIRT-3. These changes correlated with the MS heart´s mitochondrial acetylation profile. It appears that metabolic changes inherent to MS promote alterations in the expression of SIRT-3 and correlates with PTP opening sensibility.


O2k-Network Lab: MX San Pedro Garcia-Rivas G


Labels: MiParea: Respiration  Pathology: Cardiovascular, Diabetes, Other  Stress:Permeability transition  Organism: Rat 

Preparation: Isolated mitochondria 

Regulation: Calcium 



MiP2013 

Affiliations and author contributions

1 - Cátedra de Cardiología y Medicina Vascular. Escuela de Medicina. Tecnológico de Monterrey. México.

2 - Centro de Investigación Básica y Transferencia. Instituto de Cardiología y Medicina Vascular. Tec Salud del Sistema Tecnológico de Monterrey. San Pedro Garza García. México.

Email: [email protected]