title: Autophagy inhibitor 3-methyladenine alleviates overload-exercise-induced cardiac injury in rats.
abstract: Overload-exercise (OE) causes myocardial injury through inducing autophagy and apoptosis. In this study we examined whether an autophagy inhibitor 3-methyladenine (3-MA) could alleviate OE-induced cardiac injury. Rats were injected with 3-MA (15 mg/kg, iv) or saline before subjected to various intensities of OE, including no swim (control), 2 h swim (mild-intensity exercise, MIE), 2 h swim with 2.5% body weight overload (moderate OE; MOE), 5% overload (intensive OE; IOE) or 2.5% overload until exhausted (exhaustive OE; EOE). After OE, the hearts were harvested for morphological and biochemiacal analysis. The cardiac morphology, autophagosomes and apoptosis were examined with H&E staining, transmission electron microscopy and TUNEL analysis, respectively. Autophagy-related proteins to (LC3-II/I and Beclin-1) and apoptosis-related proteins (Bcl-2/Bax) were assessed using Western blotting. Our results showed that compared with the control, MIE did not change the morphological structures of the heart tissues that exhibited intact myocardial fibers and neatly arranged cardiomyocytes. However, IOE resulted in irregular arrangement of cardiomyocytes and significantly increased width of cardiomyocytes, whereas EOE caused more swollen and even disrupted cardiomyocytes. In parallel with the increased OE intensity (MOE, IOE, EOE), cardiomyocyte autophagy and apoptosis became more and more prominent, evidenced by the increasing number of autophagosomes and expression levels of LC3-II/I and Beclin-1 as well as the increasing apoptotic cells and decreasing Bcl-2/Bax ratio. 3-MA administration significantly attenuated OE-induced morphological changes of cardiomyocytes as well as all the autophagy- and apoptosis-related abnormalities in MOE, IOE and EOE rats. Thus, the autophagy inhibitor 3-MA could alleviate OE-induced heart injury in rats.
authors.affiliation: College of Health Science, Wuhan Sports University, Wuhan 430079, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Health Science, Wuhan Sports University, Wuhan 430079, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lei
authors.affiliation: College of Health Science, Shanghai University of Sport, Shanghai 200438, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pharmacology &Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA.
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: College of Health Science, Wuhan Sports University, Wuhan 430079, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.affiliation: Tongren Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Zhang-Hua
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of Pharmacology &Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Hepatobiliary Disease Institute of Wuhan University, Transplant Center of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan 430030, China.
authors.forename: Qi-Fa
authors.initials: QF
authors.lastname: Ye
authors.affiliation: College of Health Science, Wuhan Sports University, Wuhan 430079, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D004195:Disease Models, Animal; D006335:Heart Injuries / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C025946:3-methyladenine; D000225:Adenine