title: Exogenous spermine ameliorates high glucose-induced cardiomyocytic apoptosis via decreasing reactive oxygen species accumulation through inhibiting p38/JNK and JAK2 pathways.
abstract: Reactive oxygen species (ROS) generation has been suggested to play a vital role in the initiation and progression of diabetic cardiomyopathy, a major complication of diabetes mellitus. Recent studies reveal that spermine possesses proliferative, antiaging and antioxidative properties. Thus, we hypothesized that spermine could decrease apoptosis via suppressing ROS accumulation induced by high glucose (HG) in cardiomyocytes. Cultured neonatal rat ventricle cardiomyocytes were treated with normal glucose (NG) (5 mM) or HG (25 mM) in the presence or absence of spermine for 48 h. The cell activity, apoptosis, ROS production, T-SOD and GSH activities, MDA content and GSSG level were assessed. The results showed that HG induced lipid peroxidation and the increase of intracellular ROS formation and apoptosis in primary cardiomyocytes. Spermine could obviously improve the above-mentioned changes. Western blot analysis revealed that spermine markedly inhibited HG-induced the phosphorylation of p38/JNK MAPKs and JAK2. Moreover, spermine had better antioxidative and anti-apoptotic effects than N-acetyl-L-cysteine (NAC). Taken together, the present data suggested that spermine could suppress ROS accumulation to decrease cardiomyocytes apoptosis in HG condition, which may be attributed to the inhibition of p38/JNK and JAK2 activation and its natural antioxidative property. Our findings may highlight a new therapeutic intervention for the prevention of diabetic cardiomyopathy.
authors.affiliation: Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Harbin Medical University Harbin 150081, China.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Harbin Medical University Harbin 150081, China.
authors.forename: Meixiu
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D066126:Cardiotoxicity; D002478:Cells, Cultured; D019610:Cytoprotection; D005947:Glucose / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013096:Spermine / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D013096:Spermine; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; D005947:Glucose
keywords: High glucose; apoptosis; cardiomyocytes; reactive oxygen species; spermine