Onody Annamária, Zvara Agnes, Hackler László, Vígh László, Ferdinandy Péter, Puskás László G
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dóm tér 9, H-6720 Szeged, Hungary.
FEBS Lett. 2003 Feb 11;536(1-3):35-40. doi: 10.1016/s0014-5793(03)00006-1.
To profile gene expression patterns involved in ischemic preconditioning, we monitored global gene expression changes by DNA microarray analysis of 3200 rat-specific genes and by real-time quantitative polymerase chain reaction in rat hearts. Forty-nine genes with altered expression were found after ischemia/reperfusion as compared to control non-ischemic hearts and 31 genes were characteristic for classic preconditioning followed by ischemia/reperfusion as compared to ischemia/reperfusion without preconditioning. Genes with altered expression due to ischemia and/or preconditioning included those controlling protein degradation, stress responses, apoptosis, metabolic enzymes, regulatory proteins, and several unknown cellular functions. Metallothionein, natriuretic peptides, coagulation factor VII, cysteine proteinase inhibitor, peroxisome proliferator activator receptor gamma and myosin light chain kinase genes were previously suspected to be related to several cardiovascular diseases, however, most of these genes have not previously been shown to be related to myocardial ischemia/reperfusion. Some genes were observed to change specifically in response to preconditioning: oligoadenylate synthase, chaperonin subunit epsilon, a cGMP phosphodiesterase (PDE9A1), a secretory carrier membrane protein, an amino acid transporter, and protease 28 subunit. None of these genes has previously been shown to be involved in the mechanism of preconditioning.
为了描绘缺血预处理中涉及的基因表达模式，我们通过对3200个大鼠特异性基因进行DNA微阵列分析以及在大鼠心脏中进行实时定量聚合酶链反应，监测了整体基因表达变化。与对照非缺血心脏相比，缺血/再灌注后发现49个基因表达发生改变；与未进行预处理的缺血/再灌注相比，经典预处理后再进行缺血/再灌注有31个特征性基因。由于缺血和/或预处理而表达改变的基因包括那些控制蛋白质降解、应激反应、细胞凋亡、代谢酶、调节蛋白以及几种未知细胞功能的基因。金属硫蛋白、利钠肽、凝血因子VII、半胱氨酸蛋白酶抑制剂、过氧化物酶体增殖物激活受体γ和肌球蛋白轻链激酶基因先前被怀疑与几种心血管疾病有关，然而，这些基因中的大多数先前尚未被证明与心肌缺血/再灌注有关。观察到一些基因对预处理有特异性变化：寡腺苷酸合成酶、伴侣蛋白亚基ε、一种cGMP磷酸二酯酶（PDE9A1）、一种分泌载体膜蛋白、一种氨基酸转运体和蛋白酶28亚基。这些基因先前均未被证明参与预处理机制。
