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Original Article
- Basic Research
- Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy
- Guang-Yin Shen, Jeong-Hun Shin, Yi-Sun Song, Hyun-Woo Joo, In-Hwa Park, Jin-Hee Seong, Na-Kyoung Shin, A-Hyeon Lee, Young Jong Cho, Yonggu Lee, Young-Hyo Lim, Hyuck Kim, Kyung-Soo Kim
- Diabetes Metab J. 2021;45(4):594-605. Published online February 26, 2021
- DOI: https://doi.org/10.4093/dmj.2020.0049
- 11,127 View
- 174 Download
- 8 Web of Science
- 8 Crossref
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Graphical Abstract
Abstract
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Supplementary Material
PubReader 
ePub - Background
We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy.
Methods
Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit.
Results
G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro.
Conclusion
Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy. -
Citations
Citations to this article as recorded by
- K41-A enhances the antiproliferative efficacy of cisplatin in neuroblastoma by modulating apoptosis and autophagy
Gamze Sanlav, Selen Kum Ozsengezer, Zekiye Altun, Erdal Bedir, Safiye Aktas, Nur Olgun
Journal of Pharmacy and Pharmacology.2026;[Epub] CrossRef - A new macrocyclic dansyl-cyclen fluorescent probe for the identification of mildly acidic intracellular compartments
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European Journal of Pharmacology.2025; 1005: 177997. CrossRef - Targeting autophagy in diabetic cardiomyopathy: From molecular mechanisms to pharmacotherapy
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Frontiers in Pharmacology.2024;[Epub] CrossRef - Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphateâactivated protein kinase/mammalian target of the rapamycin pathway modulation
Xueyao Yang, Xin Zhao, Yanfei Liu, Yue Liu, Libo Liu, Ziyu An, Haoran Xing, Jinfan Tian, Xiantao Song
Phytotherapy Research.2023; 37(4): 1377. CrossRef - Antiatherosclerotic Effect and Molecular Mechanism of Salidroside
Si-Fan Fei, De-Bing Tong, Fang Jia
Reviews in Cardiovascular Medicine.2023;[Epub] CrossRef - Perspectives for Forkhead box transcription factors in diabetic cardiomyopathy: Their therapeutic potential and possible effects of salvianolic acids
Ronghui Han, Hemeng Huang, Weiyi Xia, Jingjin Liu, Hui Luo, Jing Tang, Zhengyuan Xia
Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
- K41-A enhances the antiproliferative efficacy of cisplatin in neuroblastoma by modulating apoptosis and autophagy
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