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Exogenous spermine ameliorates high glucose-induced cardiomyocytic apoptosis via decreasing reactive oxygen species accumulation through inhibiting p38/JNK and JAK2 pathways.
Int J Clin Exp Pathol. 2015; 8(12):15537-49.IJ

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+Show Affiliations

Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.Department of Pathophysiology, Harbin Medical University Harbin 150081, China.Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.Department of Pathophysiology, Harbin Medical University Harbin 150081, China.Department of Pathophysiology, Harbin Medical UniversityHarbin 150081, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of EducationHarbin 150081, China.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26884823

Citation

He, Yuqin, et al. "Exogenous Spermine Ameliorates High Glucose-induced Cardiomyocytic Apoptosis Via Decreasing Reactive Oxygen Species Accumulation Through Inhibiting p38/JNK and JAK2 Pathways." International Journal of Clinical and Experimental Pathology, vol. 8, no. 12, 2015, pp. 15537-49.
He Y, Yang J, Li H, et al. Exogenous spermine ameliorates high glucose-induced cardiomyocytic apoptosis via decreasing reactive oxygen species accumulation through inhibiting p38/JNK and JAK2 pathways. Int J Clin Exp Pathol. 2015;8(12):15537-49.
He, Y., Yang, J., Li, H., Shao, H., Wei, C., Wang, Y., Li, M., & Xu, C. (2015). Exogenous spermine ameliorates high glucose-induced cardiomyocytic apoptosis via decreasing reactive oxygen species accumulation through inhibiting p38/JNK and JAK2 pathways. International Journal of Clinical and Experimental Pathology, 8(12), 15537-49.
He Y, et al. Exogenous Spermine Ameliorates High Glucose-induced Cardiomyocytic Apoptosis Via Decreasing Reactive Oxygen Species Accumulation Through Inhibiting p38/JNK and JAK2 Pathways. Int J Clin Exp Pathol. 2015;8(12):15537-49. PubMed PMID: 26884823.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exogenous spermine ameliorates high glucose-induced cardiomyocytic apoptosis via decreasing reactive oxygen species accumulation through inhibiting p38/JNK and JAK2 pathways. AU - He,Yuqin, AU - Yang,Jinxia, AU - Li,Hongzhu, AU - Shao,Hongjiang, AU - Wei,Can, AU - Wang,Yuehong, AU - Li,Meixiu, AU - Xu,Changqing, Y1 - 2015/12/01/ PY - 2015/10/04/received PY - 2015/11/22/accepted PY - 2016/2/18/entrez PY - 2016/2/18/pubmed PY - 2016/11/8/medline KW - High glucose KW - apoptosis KW - cardiomyocytes KW - reactive oxygen species KW - spermine SP - 15537 EP - 49 JF - International journal of clinical and experimental pathology JO - Int J Clin Exp Pathol VL - 8 IS - 12 N2 - 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. SN - 1936-2625 UR - https://www.unboundmedicine.com/medline/citation/26884823/Exogenous_spermine_ameliorates_high_glucose_induced_cardiomyocytic_apoptosis_via_decreasing_reactive_oxygen_species_accumulation_through_inhibiting_p38/JNK_and_JAK2_pathways_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26884823/ DB - PRIME DP - Unbound Medicine ER -