Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats

被引:82
作者
Cheng, Shiu-Min [1 ]
Ho, Tsung-Jung [2 ,3 ]
Yang, Ai-Lun [4 ]
Chen, I-Ju [5 ]
Kao, Chung-Lan [6 ,7 ]
Wu, Fan-Ni [8 ]
Lin, James A. [8 ]
Kuo, Chia-Hua [9 ,10 ]
Ou, Hsiu-Chung [10 ]
Huang, Chih-Yang [2 ,8 ,11 ]
Lee, Shin-Da [10 ,12 ]
机构
[1] Asia Univ, Dept Psychol, Taichung, Taiwan
[2] China Med Univ, Coll Chinese Med, Sch Chinese Med, Taichung 40202, Taiwan
[3] China Med Univ, Beigang Hosp, Chinese Med Dept, Taichung 40202, Yunlin County, Taiwan
[4] Taipei Phys Educ Coll, Dept Sports Sci, Taipei, Taiwan
[5] Asia Univ, Dept Phys Educ, Taichung, Taiwan
[6] Taipei Vet Gen Hosp, Dept Phys Med & Rehabil, Taipei, Taiwan
[7] Natl Yang Ming Univ, Taipei 112, Taiwan
[8] China Med Univ, Grad Inst Basic Med Sci, Taichung 40202, Taiwan
[9] Taipei Phys Educ Coll, Lab Exercise Biochem, Taipei, Taiwan
[10] China Med Univ, Grad Inst Rehabil Sci, Dept Phys Therapy, Taichung 40202, Taiwan
[11] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung, Taiwan
[12] Asia Univ, Dept Healthcare Adm, Taichung, Taiwan
关键词
Apoptosis; Bcl-2; Diabetes; Heart; IGFI-R/PI3K/Akt survival pathway; GROWTH-FACTOR-I; CARDIOMYOCYTE APOPTOSIS; HEART-FAILURE; PHYSICAL-ACTIVITY; CYTOCHROME-C; INSULIN; HYPERTROPHY; KINASE; SKELETAL; DEATH;
D O I
10.1016/j.ijcard.2012.01.031
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Increased myocyte apoptosis in diabetic hearts has been previously reported. The purpose of this study was to evaluate the effects of exercise training on cardiac survival pathways in streptozotocin (STZ)-induced diabetic rats. Methods: Forty-eight male Wistar rats were randomly divided into control group (Control), STZ-induced (65 mg/kg, i.p.) diabetes (DM), and DM rats with moderate aerobic exercise training (DM-EX) on a treadmill 60 min/day, 5 days/week, for 10 weeks. Histopathological analysis, positive TUNEL assays and Western blotting were performed on the excised cardiac left ventricles from all three groups. Results: The components of cardiac survival pathway (insulin-like growth factor I (IGFI), IGFI-receptor (IGFI-R), phosphatidylinositol 3'-kinase (PI3K), and Akt) and the pro-survival Bcl-2 family proteins (Bcl-2, Bcl-xL, and p-BAD) were all significantly decreased in the DM group compared with the Control group whereas they were increased in the DM-EX group. In addition, the abnormal myocardial architecture, enlarged interstitial space and increased cardiac TUNEL-positive apoptotic cells were observed in the DM group, but they were reduced in the DM-EX group. The apoptotic key component, caspase-3, was significantly increased in the DM group relative to the Control group whereas it was decreased in the DM-EX group. Conclusions: Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways, which provides one of the new beneficial effects for exercise training in diabetes. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:478 / 485
页数:8
相关论文
共 37 条
[1]   Hypertensive end-organ damage and premature mortality are p38 mitogen-activated protein kinase-dependent in a rat model of cardiac hypertrophy and dysfunction [J].
Behr, TM ;
Nerurkar, SS ;
Nelson, AH ;
Coatney, RW ;
Woods, TN ;
Sulpizio, A ;
Chandra, S ;
Brooks, DP ;
Kumar, S ;
Lee, JC ;
Ohlstein, EH ;
Angermann, CE ;
Adams, JL ;
Sisko, J ;
Sackner-Bernstein, JD ;
Willette, RN .
CIRCULATION, 2001, 104 (11) :1292-1298
[2]   Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies [J].
Bernardo, Bianca C. ;
Weeks, Kate L. ;
Pretorius, Lynette ;
McMullen, Julie R. .
PHARMACOLOGY & THERAPEUTICS, 2010, 128 (01) :191-227
[3]  
Bishopric Nanette H., 2001, Current Opinion in Pharmacology, V1, P141, DOI 10.1016/S1471-4892(01)00032-7
[4]   Mitochondrial uncoupling: A key contributor to reduced cardiac efficiency in diabetes [J].
Boudina, Sihem ;
Abel, E. Dale .
PHYSIOLOGY, 2006, 21 :250-258
[5]   Nitric oxide, cytochrome c and mitochondria [J].
Brown, GC ;
Borutaite, V .
MITOCHONDRIA AND CELL DEATH, 1999, 66 :17-25
[6]  
Colberg SR, 2007, CURR DIABETES REV, V3, P176
[7]   Cardiovascular control in experimental diabetes [J].
De Angelis, K ;
Schaan, BD ;
Maeda, CY ;
Dall'Ago, P ;
Wichi, RB ;
Irigoyen, MC .
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 2002, 35 (09) :1091-1100
[8]   Effects of Exercise Training on Health Status in Patients With Chronic Heart Failure HF-ACTION Randomized Controlled Trial [J].
Flynn, Kathryn E. ;
Pina, Ileana L. ;
Whellan, David J. ;
Lin, Li ;
Blumenthal, James A. ;
Ellis, Stephen J. ;
Fine, Lawrence J. ;
Howlett, Jonathan G. ;
Keteyian, Steven J. ;
Kitzman, Dalane W. ;
Kraus, William E. ;
Miller, Nancy Houston ;
Schulman, Kevin A. ;
Spertus, John A. ;
O'Connor, Christopher M. ;
Weinfurt, Kevin P. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 301 (14) :1451-1459
[9]   Myocardial cell death in human diabetes [J].
Frustaci, A ;
Kajstura, J ;
Chimenti, C ;
Jakoniuk, I ;
Leri, A ;
Maseri, A ;
Nadal-Ginard, B ;
Anversa, P .
CIRCULATION RESEARCH, 2000, 87 (12) :1123-1132
[10]   Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion [J].
Ghosh, S ;
Pulinilkunnil, T ;
Yuen, G ;
Kewalramani, G ;
An, D ;
Qi, D ;
Abrahani, A ;
Rodrigues, B .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 289 (02) :H768-H776