Contradictory effects of short- and long-term hyperglycemias on ischemic injury of myocardium via intracellular signaling pathway

被引:54
作者
Xu, G [1 ]
Takashi, E [1 ]
Kudo, M [1 ]
Ishiwata, T [1 ]
Naito, Z [1 ]
机构
[1] Nippon Med Coll, Dept Pathol 2, Bunkyo Ku, Tokyo 1138602, Japan
关键词
hyperglycemia; myocardial infarction; sensitivity of ischemic injury; ERK1/2; apoptosis;
D O I
10.1016/j.yexmp.2003.08.003
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Although clinical diabetes mellitus is obviously a high risk factor for myocardial infarction, there is disagreement about the sensitivity of ischemic injury of an infarcted myocardium in experimental studies. The present study evaluated the influences of different durations of hyperglycemia on ischemic and reperfusion injuries of the myocardium, and focused on extracellular signal-regulated kinase 1/2 (ERK1/2), which plays an important role in the intracellular signaling pathway and is reported to be associated with myocardial protection against heart injury. Short- and long-term hyperglycemias were induced in rats by streptozotocin (STZ) injection and the rats were examined 4 (4WDM) and 20 weeks (20WDM) after the treatment. Ischemia and reperfusion were induced by occlusion and reperfusion (I/R) of the left coronary artery (LCA). I/R-induced infarct size was determined using triphenyltetrazolium chloride (TTC) staining. After 20 weeks of STZ treatment (20WDM + I/R), the infarct size in the rat heart increased by 65.2 +/- 4.3%, whereas after 4 weeks of STZ treatment (4WDM + I/R), the infarct size decreased compared with the time-matched I/R group (43.1 +/- 3.6% and 59.5 +/- 5.6%, respectively). The number of dead myocytes including necrotic and apoptotic cells was determined using horseradish peroxidase (HRP) and terminal deoxynucleotide nick-end labeling (TUNEL) methods. The number of dead myocytes decreased in the 4WDM+I/R group, while the number of dead myocytes increased markedly in the 20WDM + I/R group, compared with the time-matched I/R group. The increment of ERK 1/2 phosphorylation in the 4WDM group and the slight enhancement of this phosphorylation by I/R treatment were observed by western blotting. However, in the 20WDM group, the level of ERK1/2 phosphorylation reduced by approximately 1/3 compared with the time-matched control group; moreover, I/R treatment did not enhance the phosphorylation level. This study demonstrated that short- and long-term hyperglycemias exert opposite influences on ischemic myocardial injury, and these contradictory influences may depend on an ERK1/2-mediated intracellular signaling pathway. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:57 / 65
页数:9
相关论文
共 35 条
[1]   Oxidative stress activates extracellular signal-regulated kinases through Src and ras in cultured cardiac myocytes of neonatal rats [J].
Aikawa, R ;
Komuro, I ;
Yamazaki, T ;
Zou, YZ ;
Kudoh, S ;
Tanaka, M ;
Shiojima, I ;
Hiroi, Y ;
Yazaki, Y .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (07) :1813-1821
[2]  
Awazu M, 1999, J AM SOC NEPHROL, V10, P738
[3]   DECREASED EXPRESSION OF PROTEIN-KINASE-C ALPHA,BETA, AND EPSILON IN SOLEUS MUSCLE OF ZUCKER OBESE (FA/FA) RATS [J].
COOPER, DR ;
WATSON, JE ;
DAO, ML .
ENDOCRINOLOGY, 1993, 133 (05) :2241-2247
[4]  
DAVIS RJ, 1993, J BIOL CHEM, V268, P14553
[5]   DIABETIC CARDIOMYOPATHY [J].
FEIN, FS ;
SONNENBLICK, EH .
PROGRESS IN CARDIOVASCULAR DISEASES, 1985, 27 (04) :255-270
[6]   More than one way to die: apoptosis, necrosis and reactive oxygen damage [J].
Fiers, W ;
Beyaert, R ;
Declercq, W ;
Vandenabeele, P .
ONCOGENE, 1999, 18 (54) :7719-7730
[7]   Myocyte death in streptozotocin-induced diabetes in rats is angiotensin II-dependent [J].
Fiordaliso, F ;
Li, BS ;
Latini, R ;
Sonnenblick, EH ;
Anversa, P ;
Leri, A ;
Kajstura, J .
LABORATORY INVESTIGATION, 2000, 80 (04) :513-527
[8]   ACUTE MYOCARDIAL-INFARCTION IN DOGS WITH EXPERIMENTAL DIABETES [J].
FORRAT, R ;
SEBBAG, L ;
WIERNSPERGER, N ;
GUIDOLLET, J ;
RENAUD, S ;
DELORGERIL, M .
CARDIOVASCULAR RESEARCH, 1993, 27 (11) :1908-1912
[9]  
Fryer RM, 2001, J PHARMACOL EXP THER, V296, P642
[10]   CALCIUM-DEPENDENT PROTEIN-KINASE ACTIVITY IS DECREASED IN DIABETIC RAT SCIATIC-NERVE [J].
GABBAY, RA ;
SICONOLFIBAEZ, L ;
LEBOVITZ, HE .
ENDOCRINOLOGY, 1990, 127 (03) :1194-1198