|
KMID : 1200020210450040594
|
|
Diabetes & Metabolism Journal
2021 Volume.45 No. 4 p.594 ~ p.605
|
|
|
Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy
|
|
Shen Guang-Yin
Shin Jeong-Hun
Song Yi-Sun
Joo Hyun-Woo
Park In-Hwa
Seong Jin-Hee
Shin Na-Kyoung
Lee A-Hyeon
Cho Young-Jong
Lee Yong-Gu
Lim Young-Hyo
Kim Hyuck
Kim Kyung-Soo
|
|
|
Abstract
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Apoptosis, Autophagy, Diabetic cardiomyopathies, Granulocyte colony-stimulating factor, Myocytes, cardiac
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
   
|
|