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
[11]   Apoptosis - Basic mechanisms and implications for cardiovascular disease [J].
Haunstetter, A ;
Izumo, S .
CIRCULATION RESEARCH, 1998, 82 (11) :1111-1129
[12]   Insulin-like growth factor-1 protects H9c2 cardiac myoblasts from oxidative stress-induced apoptosis via phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways [J].
Hong, F ;
Kwon, SJ ;
Jhun, BS ;
Kim, SS ;
Ha, J ;
Kim, SJ ;
Sohn, NW ;
Kang, C ;
Kang, I .
LIFE SCIENCES, 2001, 68 (10) :1095-1105
[13]   Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy [J].
Konhilas, JP ;
Watson, PA ;
Maass, AH ;
Boucek, DM ;
Horn, T ;
Stauffer, BL ;
Luckey, SW ;
Rosenberg, P ;
Leinwand, LA .
CIRCULATION RESEARCH, 2006, 98 (04) :540-548
[14]   Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3 [J].
Kubasiak, LA ;
Hernandez, OM ;
Bishopric, NH ;
Webster, KA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12825-12830
[15]   Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin-induced diabetic rats [J].
Kuo, Wei-Wen ;
Chung, Li-Ching ;
Liu, Cheng-Tzu ;
Wu, Shih-Ping ;
Kuo, Chia-Hua ;
Tsai, Fuu-Jen ;
Tsai, Chang-Hai ;
Lu, Min-Chi ;
Huang, Chih-Yang ;
Lee, Shin-Da .
CELL BIOCHEMISTRY AND FUNCTION, 2009, 27 (07) :479-487
[16]   Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart [J].
Kwak, Hyo-Bum ;
Song, Wook ;
Lawler, John M. .
FASEB JOURNAL, 2006, 20 (02) :791-+
[17]   Roles of insulin-like growth factor II in cardiomyoblast apoptosis and in hypertensive rat heart with abdominal aorta ligation [J].
Lee, Shin-Da ;
Chu, Chun-Hsien ;
Huang, Erh-Jung ;
Lu, Min-Chi ;
Liu, Jer-Yuh ;
Liu, Chung-Jung ;
Hsu, Hsi-Hsien ;
Lin, James A. ;
Kuo, Wei-Wen ;
Huang, Chih-Yang .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2006, 291 (02) :E306-E314
[18]   Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c [J].
Liu, XS ;
Kim, CN ;
Yang, J ;
Jemmerson, R ;
Wang, XD .
CELL, 1996, 86 (01) :147-157
[19]   The role of immune and inflammatory processes in the development of macrovascular disease in diabetes [J].
Lopes-Virella, MF ;
Virella, G .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2003, 8 :S750-S768
[20]   Diabetes mellitus and heart failure: Epidemiology, mechanisms, and pharmacotherapy [J].
Masoudi, Frederick A. ;
Inzucchi, Silvio E. .
AMERICAN JOURNAL OF CARDIOLOGY, 2007, 99 (4A) :113B-132B