Edison Biotechnology Institute and Dept. of Biomedical Sciences, Ohio University, 1 Water Tower Drive, The Ridges, Athens, OH 45701, USA.
J Proteomics. 2011 May 1;74(5):716-27. doi: 10.1016/j.jprot.2011.02.018. Epub 2011 Feb 24.
The development of type 2 diabetes (T2D) is strongly associated with obesity. In humans, T2D increases the risk for end organ complications. Among these, heart disease has been ranked as the leading cause of death. We used a proteomic methodology to test the hypothesis that a pre-diabetic state generated by high-fat diet leads to changes in proteins related to heart function and structure. Over 300 protein spots were resolved by two-dimensional gel electrophoresis (2-DE). Fifteen protein spots were found to be altered (7 decreased and 8 increased) in pre-diabetic hearts. The protein spots were then identified by mass spectrometry and immunoblots. Among the decreased proteins, 3 are involved in heart structure (one isoform of desmin, troponin T2 and α-cardiac actin), 3 are involved in energy metabolism (mitochondrial ATP synthase β subunit, adenylate kinase and creatine kinase) and one is a component of the citric acid cycle (isocitrate dehydrogenase 3). In contrast, proteins involved in fatty acid oxidation (two isoforms of peroxisomal enoyl-CoA hydratase) and the citric acid cycle (three isoforms of malate dehydrogenase) were increased in pre-diabetic hearts. The results suggest that changes in the levels of several heart proteins may have implications in the development of the cardiac phenotype associated to T2D.
2 型糖尿病（T2D）的发展与肥胖密切相关。在人类中，T2D 增加了终末器官并发症的风险。其中，心脏病已被列为主要死亡原因。我们使用蛋白质组学方法来检验以下假设，即高脂肪饮食引起的糖尿病前期状态会导致与心脏功能和结构相关的蛋白质发生变化。通过二维凝胶电泳（2-DE）解析了超过 300 个蛋白质斑点。在糖尿病前期心脏中发现 15 个蛋白质斑点发生改变（7 个减少，8 个增加）。然后通过质谱和免疫印迹法鉴定蛋白质斑点。在减少的蛋白质中，有 3 种涉及心脏结构（一种结蛋白同工型、肌钙蛋白 T2 和α-心脏肌动蛋白），3 种涉及能量代谢（线粒体 ATP 合酶β亚基、腺苷酸激酶和肌酸激酶），1 种是柠檬酸循环的组成部分（异柠檬酸脱氢酶 3）。相比之下，在糖尿病前期心脏中，参与脂肪酸氧化（两种过氧化物酶体烯酰辅酶 A 水合酶同工型）和柠檬酸循环（三种苹果酸脱氢酶同工型）的蛋白质增加。结果表明，几种心脏蛋白水平的变化可能对与 T2D 相关的心脏表型的发展有影响。
