RESUMO
OBJECTIVE: Impaired mitochondrial function may contribute to the onset of contractile dysfunction with insulin resistance/type 2 diabetes. Our aim was therefore to determine alterations in the mitochondrial proteome of a mouse model of obesity/type 2 diabetes. METHODS: Mitochondrial proteins were isolated from hearts collected from 18- to 20-week-old female db/db mice and compared to matched controls. We performed two-dimensional polyacrylamide gel electrophoresis to determine differentially expressed proteins. Peptides of interest were further analysed by mass spectrometry and Mascot software was employed to identify protein matches. RESULTS: Our data showed that ATP synthase D chain, ubiquinol cytochrome-C reductase core protein 1 and electron transfer flavoprotein subunit alpha peptide levels were altered with obesity. Moreover, we found coordinate downregulation of contractile proteins in the obese heart, i.e. α-smooth muscle actin, α-cardiac actin, myosin heavy-chain α and myosin-binding protein C. CONCLUSION: We propose that decreased contractile protein levels may contribute to contractile dysfunction of hearts from diabetic mice.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Mitocôndrias Cardíacas/metabolismo , Proteínas Mitocondriais/metabolismo , Miocárdio/metabolismo , Obesidade/metabolismo , Proteômica , Animais , Proteínas Contráteis/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Eletroforese em Gel Bidimensional , Metabolismo Energético , Feminino , Camundongos , Camundongos Knockout , Contração Miocárdica , Obesidade/genética , Proteômica/métodos , Receptores para Leptina/deficiência , Receptores para Leptina/genética , Software , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The effect of the addition of a radio-opaque filler, barium sulfate (BaSO(4)), on the mechanical properties of a biodegradable amorphous polymer film (poly-lactic-co-glycolic acid, PLGA) was studied, as a function of degradation. With up to about 18% loading (v/v), the modulus of the filled polymer increases; beyond this concentration, agglomerates are formed. The filled systems are also radio-opaque, over a thickness range of 0.07-0.19 mm in stent form (helicoidal). These stents were then immersed in phosphate buffer pH 7.4 at 37(o)C for 2 weeks. The radial strength of stent was measured by using a compression test. It was found that filler-loaded stent (FS) increased in radial strength by about 4 times (14.95 +/- 1.20 N/mm) compared to the unfilled stent (UFS). However, both samples lost radial strength as the polymer degraded in buffer, but FS retained 60% (9.05 +/- 0.07 N/mm) of its strength after 2 weeks whereas only 36% (1.39 +/- 1.04 N/mm) was retained for UFS. Moreover, UFS lost its helical shape after 3 weeks. The findings have implications for optimization of degradable stent formulations.
