Banca de QUALIFICAÇÃO: CICERA ÉDNA BARBOSA DAVID

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : CICERA ÉDNA BARBOSA DAVID
DATA : 17/01/2019
HORA: 14:00
LOCAL: Faculdade de Medicina
TÍTULO:

Evaluation of the effects of mitochondrial ATP sensitive potassium channel on cardiac hypertrophy in mice submitted to calorie restriction

PALAVRAS-CHAVES:

Cardiac hypertrophy. Caloric Restriction. Mitochondrion. Reactive Oxigen Species. Mitochondrial ATP-sensitive K+ channel.

PÁGINAS: 70
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
SUBÁREA: Metabolismo e Bioenergética
RESUMO:

Cardiac hypertrophy is a compensatory response of the heart to an increase in afterload. Although it is a temporary beneficial response, it often leads to cardiomyopathy and con-gestive heart failure. Caloric restriction (CR) is a powerful intervention to improve health and delay aging. Mitochondria have an ATP-sensitive K+ channels (mitoKATP), whose opening leads to cellular protection through mechanisms related to the reduction of cellu-lar oxidative stress. Here, we investigated whether calorie restriction in mice prevented isoproterenol-induced cardiac hypertrophy in vivo by avoiding reactive oxygen species (ROS) production and maintaining antioxidant enzymatic activity. Additionally, we inves-tigated the involvement of mitochondrial ATPsensitive K+ channels (mitoKATP) in cardiac hypertrophy. Thus, mice (Mus musculus) Swiss were fed a standard diet of rodents ad libitum for 2 weeks and then randomly divided into two groups: ad libitum (AL group) fed with 60% of the average calorie intake RC) for an additional 4 weeks. To induce cardiac hypertrophy, mice were treated with isoproterenol (ISO) (30 mg / kg / day) and mitoKATP blockers , 5-hydroxydecanoate (5-HD) (10 mg / kg / day) and glibenclamide (GLY) 6 mg/ kg / day) for 8 days. Isoproterenol-treated mice had elevated heart weight/tibia length ratios and cardiac protein levels. These gross hypertrophic markers were significantly reduced in CR mice. Cardiac tissue from isoproterenol-treated CR mice also produced less H2O2 and had lower protein sulfydryl oxidation. Additionally, calorie restriction blo-cked hypertrophic-induced antioxidant enzyme (catalase, superoxide dismutase and glu-tathione peroxidase) activity repression during cardiac hypertrophy. MitoKATP opening was repressed in isolated mitochondria from hypertrophic hearts, in a manner sensitive to calorie restriction. Finally, mitoKATP inhibition significantly blocked the protective ef-fects of calorie restriction. Altogether, our results suggest that CR improves intracellular redox balance during cardiac hypertrophy and prevents this process in a mechanism involving mitoKATP activation.

MEMBROS DA BANCA:
Presidente - 2185176 - FRANCISCO NASCIMENTO PEREIRA JUNIOR
Interno - 2353800 - CLAUDIO GLEIDISTON LIMA DA SILVA
Externo à Instituição - HENRIQUE DOUGLAS MELO COUTINHO - URCA