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Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of glycogen synthase kinase-3β.
Biosci Rep. 2019 01 31; 39(1)BR

Abstract

To evaluate the role of glycogen synthase kinase-3β (GSK-3β) in the apoptosis of cardiomyocytes in diabetic cardiomyopathy (DCM). Diabetes mellitus (DM) in rats was induced by intraperitoneal injection of 1% streptozotocin (STZ), and lithium chloride (LiCl) was used to decrease the expression of GSK-3β. Hematoxylin/eosin (HE) staining and the terminal deoxyribonucleotide transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay was conducted to evaluate the pathological injury and apoptosis of cardiomyocytes respectively. Western blot was applied to detect the protein expressions of Cleaved-caspase 3, caspase 3, Bax and Bcl-2 in rat cardiomyocytes. Real-time polymerase chain reaction (RT-PCR) was applied to detect the gene expressions of phosphoinositide 3-kinases (PI3K), Akt, and GSK-3β in rat cardiomyocytes. DM-induced cardiomyocyte injuries, which were presented as capillary basement membrane thickening, interstitial fibrosis, cardiomyocyte hypertrophy and necrosis in HE staining and increased apoptosis detected by TUNEL assay. When comparing with the control group, the mRNA expression of PI3K and Akt in DM group obviously decreased but the mRNA expression of GSK-3β obviously elevated (P < 0.05). In addition, the ratio of Cleaved-caspase 3/caspase 3 and Bax/Bcl-2 were notably increased in DM group compared with control group (P < 0.05). LiCl, as an inhibitor of GSK-3 apparently reduced the expression of GSK-3β mRNA (P < 0.05) but not the PI3K and Akt comparing with the DM group. LiCl also attenuated the myocardial injury and apoptosis induced by DM. The myocardial injury induced by DM is associated with the up-regulation of GSK-3β. LiCl inhibited the expression of GSK-3β and myocardial apoptosis in diabetic myocardium.

Authors+Show Affiliations

Emergency Medicine, The First Hospital of China Medical University, Shenyang Liaoning Province, China bunnken36@sohu.com.Emergency Medicine, The First Hospital of China Medical University, Shenyang Liaoning Province, China.Emergency Medicine, The First Hospital of China Medical University, Shenyang Liaoning Province, China.

Pub Type(s)

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

Language

eng

PubMed ID

30237226

Citation

Wu, Wei, et al. "Apoptosis of Cardiomyocytes in Diabetic Cardiomyopathy Involves Overexpression of Glycogen Synthase Kinase-3β." Bioscience Reports, vol. 39, no. 1, 2019.
Wu W, Liu X, Han L. Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of glycogen synthase kinase-3β. Biosci Rep. 2019;39(1).
Wu, W., Liu, X., & Han, L. (2019). Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of glycogen synthase kinase-3β. Bioscience Reports, 39(1). https://doi.org/10.1042/BSR20171307
Wu W, Liu X, Han L. Apoptosis of Cardiomyocytes in Diabetic Cardiomyopathy Involves Overexpression of Glycogen Synthase Kinase-3β. Biosci Rep. 2019 01 31;39(1) PubMed PMID: 30237226.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of glycogen synthase kinase-3β. AU - Wu,Wei, AU - Liu,Xingxing, AU - Han,Longfei, Y1 - 2019/01/03/ PY - 2017/09/28/received PY - 2018/08/08/revised PY - 2018/08/20/accepted PY - 2018/9/22/pubmed PY - 2019/7/28/medline PY - 2018/9/22/entrez KW - Phosphoinositide 3-kinases KW - apoptosis KW - diabetic cardiomyopathy KW - glycogen synthase kinase-3β JF - Bioscience reports JO - Biosci. Rep. VL - 39 IS - 1 N2 - To evaluate the role of glycogen synthase kinase-3β (GSK-3β) in the apoptosis of cardiomyocytes in diabetic cardiomyopathy (DCM). Diabetes mellitus (DM) in rats was induced by intraperitoneal injection of 1% streptozotocin (STZ), and lithium chloride (LiCl) was used to decrease the expression of GSK-3β. Hematoxylin/eosin (HE) staining and the terminal deoxyribonucleotide transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay was conducted to evaluate the pathological injury and apoptosis of cardiomyocytes respectively. Western blot was applied to detect the protein expressions of Cleaved-caspase 3, caspase 3, Bax and Bcl-2 in rat cardiomyocytes. Real-time polymerase chain reaction (RT-PCR) was applied to detect the gene expressions of phosphoinositide 3-kinases (PI3K), Akt, and GSK-3β in rat cardiomyocytes. DM-induced cardiomyocyte injuries, which were presented as capillary basement membrane thickening, interstitial fibrosis, cardiomyocyte hypertrophy and necrosis in HE staining and increased apoptosis detected by TUNEL assay. When comparing with the control group, the mRNA expression of PI3K and Akt in DM group obviously decreased but the mRNA expression of GSK-3β obviously elevated (P < 0.05). In addition, the ratio of Cleaved-caspase 3/caspase 3 and Bax/Bcl-2 were notably increased in DM group compared with control group (P < 0.05). LiCl, as an inhibitor of GSK-3 apparently reduced the expression of GSK-3β mRNA (P < 0.05) but not the PI3K and Akt comparing with the DM group. LiCl also attenuated the myocardial injury and apoptosis induced by DM. The myocardial injury induced by DM is associated with the up-regulation of GSK-3β. LiCl inhibited the expression of GSK-3β and myocardial apoptosis in diabetic myocardium. SN - 1573-4935 UR - https://www.unboundmedicine.com/medline/citation/30237226/Apoptosis_of_cardiomyocytes_in_diabetic_cardiomyopathy_involves_overexpression_of_glycogen_synthase_kinase_3β_ L2 - https://portlandpress.com/bioscirep/article-lookup/doi/10.1042/BSR20171307 DB - PRIME DP - Unbound Medicine ER -