Institute of Pharmacology, University of Aarhus, Århus C, Denmark.
Mol Cell Biochem. 2012 Jan;360(1-2):353-62. doi: 10.1007/s11010-011-1075-z. Epub 2011 Oct 1.
AMP-activated protein kinase (AMPK) is an enzyme which may be involved in cardioprotective mechanisms in the ischemic heart. Exercise, AICAR, and metformin, all known activators of AMPK, induce delayed cardioprotection which protects the heart against ischemia-reperfusion injury. The objective was to determine the effect of exercise, AICAR, and metformin on gene expression profile and to demonstrate possible interactions in different genes and functions. Rats were divided into either an exercise, AICAR, metformin, or control group. 3, 12, and 24 h after either a single bout of exercise training, a single injection of AICAR or a single dose of metformin, hearts were removed and gene expression profiles were analyzed in tissue from the left ventricle using Affymetrix gene chip probe arrays. Ingenuity Pathway Analysis (IPA) tool was used to analyze the regulated genes for relevant functions and diseases. Each gene chip identified up to 30,000 different probesets of which Ingenuity identified approximately up to 12,000 genes. A total of 147, 304, and 114 different genes in the left ventricle whose expressions were altered >2.0-fold were identified in the exercise, AICAR, and metformin group, respectively. Seventy eight different genes were overlapping the exercise and AICAR group at 24 h. Ingenuity identified six overlapping genes between the exercise, AICAR, and metformin groups including NR4A3, TNFRSF12A, HBB, PENK, PAP, and MAP4K4. IPA software revealed an overabundance of focus molecules in all three intervention groups involving functions related to cell death, cellular growth and proliferation, gene expression and cancer. Exercise, AICAR, and metformin regulate several genes in the rat myocardium with the majority of overlapping genes observed in the exercise and AICAR group. Changes in gene programming mainly involved inflammatory and opioid systems recognized as cardioprotective pathways. Some of these genes may represent possible candidate genes involved in the molecular mechanisms of AMPK-induced delayed PC.
腺苷酸活化蛋白激酶（AMPK）可能参与缺血性心脏的心脏保护机制。运动、AICAR 和二甲双胍，均为 AMPK 的已知激活剂，可诱导延迟性心脏保护，防止心脏发生缺血再灌注损伤。本研究旨在确定运动、AICAR 和二甲双胍对基因表达谱的影响，并证明不同基因和功能之间可能存在相互作用。将大鼠分为运动组、AICAR 组、二甲双胍组和对照组。单次运动训练、单次 AICAR 注射或单次二甲双胍给药后 3、12 和 24 h，取出心脏，使用 Affymetrix 基因芯片探针阵列分析左心室组织的基因表达谱。采用 IPA 工具分析相关功能和疾病的调节基因。每个基因芯片最多可识别 30000 个不同的探针，IPA 可识别大约 12000 个基因。运动组、AICAR 组和二甲双胍组左心室中分别有 147、304 和 114 个基因的表达改变超过 2.0 倍。24 h 时，运动组和 AICAR 组有 78 个不同的基因重叠。IPA 鉴定了运动组、AICAR 组和二甲双胍组之间的 6 个重叠基因，包括 NR4A3、TNFRSF12A、HBB、PENK、PAP 和 MAP4K4。IPA 软件显示，所有三组干预措施中均存在大量焦点分子，涉及细胞死亡、细胞生长和增殖、基因表达和癌症等功能。运动、AICAR 和二甲双胍调节大鼠心肌中的多个基因，运动组和 AICAR 组观察到的重叠基因最多。基因编程的变化主要涉及炎症和阿片系统，这些系统被认为是心脏保护途径。其中一些基因可能代表 AMPK 诱导的延迟性 PC 分子机制中可能的候选基因。
