RESUMEN
The aim of the present study was to examine the role of sirtuin 3 (Sirt3)autophagy in regulating myocardial energy metabolism and inhibiting myocardial hypertrophy in angiotensin (Ang) IIinduced myocardial cell hypertrophy. The primary cultured myocardial cells of neonatal Sprague Dawley rats were used to construct a myocardial hypertrophy model induced with Ang II. Following the activation of Sirt3 by resveratrol (Res), Sirt3 was silenced using small interfering (si)RNASirt3, and the morphology of the myocardial cells was observed under an optical microscope. Reverse transcriptionpolymerase chain reaction was used to detect the mRNA expression of the following myocardial hypertrophy markers; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), Sirt3, mediumchain acylCoA dehydrogenase (MCAD) and pyruvate kinase (PK). Western blot analysis was used to detect the protein expression of Sirt3, light chain 3 (LC3) and Beclin1. Ang II may inhibit the protein expression of Sirt3, LC3 and Beclin1. Res, an agonist of Sirt3, may promote the protein expression of Sirt3, LC3 and Beclin1. Res inhibited the mRNA expression of ANP and BNP, and reversed the Ang IIinduced myocardial cell hypertrophy. The addition of siRNASirt3 decreased the protein expression of Sirt3, LC3 and Beclin1, increased the mRNA expression of ANP and BNP, and weakened the inhibitory effect of Res on myocardial cell hypertrophy. Res promoted the mRNA expression of MCAD, inhibited the mRNA expression of PK, and reversed the influence of Ang II on myocardial energy metabolism. siRNASirt3 intervention significantly decreased the effect of Res in eliminating abnormal myocardial energy metabolism. In conclusion, Sirt3 may inhibit Ang IIinduced myocardial hypertrophy and reverse the Ang IIcaused abnormal myocardial energy metabolism through activation of autophagy.
Asunto(s)
Autofagia/efectos de los fármacos , Cardiomegalia/metabolismo , Metabolismo Energético/fisiología , Resveratrol/farmacología , Sirtuinas/metabolismo , Acil-CoA Deshidrogenasa/metabolismo , Angiotensina II/toxicidad , Animales , Animales Recién Nacidos , Factor Natriurético Atrial/metabolismo , Beclina-1/metabolismo , Cardiomegalia/inducido químicamente , Células Cultivadas , Femenino , Silenciador del Gen , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Péptido Natriurético Encefálico/metabolismo , Piruvato Quinasa/metabolismo , Ratas Sprague-Dawley , Sirtuinas/efectos de los fármacos , Sirtuinas/genéticaRESUMEN
The present report investigated the correlation between the expression levels of matrix metalloproteinase (MMP)-9 in gastric carcinoma patients and the clinicopathological characteristics. Forty-five samples of gastric carcinoma and distal gastric mucosa tissue, and 10 samples of healthy gastric mucosa tissue were analyzed using semi-quantitative polymerase chain reaction, as well as immunohistochemical and hematoxylin and eosin staining. MMP-9 protein levels in serum samples from the same patients were quantified by enzyme-linked immunosorbent assay. The present report identified that MMP-9 expression was markedly higher in the gastric carcinoma tissue (86.67%) than in the adjacent healthy tissue (10.00%). A positive association was identified between the level of MMP-9 protein expression and the depth of cancer invasion (P<0.05). Furthermore, the preoperative serum levels of the MMP-9 protein in the gastric carcinoma tissue were correlated with the tumor-node-metastasis stage and occurrence of lymph node metastasis (P<0.01). Data from the present report indicates that MMP-9 may be key in gastric carcinoma malignancy, and implies that MMP-9 may serve as a novel biomarker in the diagnosis and prognosis of gastric carcinoma.
