Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial IschemiaReperfusion Injury via Mitochondria Apoptosis Pathway
Joint Authors
Xue, Rui
Wu, Yang
Meng, Qing-Tao
Zhao, Bo
Leng, Yan
Zhan, Li-ying
Xia, Zhongyuan
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-01-16
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Background.
Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology.
Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts.
We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury.
Methods.
Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion.
H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R).
Results.
Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity.
MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA).
TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis.
Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro.
Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression.
Conclusions.
Both diabetes mellitus and MI/R injury increased cardiac HDACs activity.
Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim.
American Psychological Association (APA)
Wu, Yang& Leng, Yan& Meng, Qing-Tao& Xue, Rui& Zhao, Bo& Zhan, Li-ying…[et al.]. 2017. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial IschemiaReperfusion Injury via Mitochondria Apoptosis Pathway. Journal of Diabetes Research،Vol. 2017, no. 2017, pp.1-15.
https://search.emarefa.net/detail/BIM-1174816
Modern Language Association (MLA)
Wu, Yang…[et al.]. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial IschemiaReperfusion Injury via Mitochondria Apoptosis Pathway. Journal of Diabetes Research No. 2017 (2017), pp.1-15.
https://search.emarefa.net/detail/BIM-1174816
American Medical Association (AMA)
Wu, Yang& Leng, Yan& Meng, Qing-Tao& Xue, Rui& Zhao, Bo& Zhan, Li-ying…[et al.]. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial IschemiaReperfusion Injury via Mitochondria Apoptosis Pathway. Journal of Diabetes Research. 2017. Vol. 2017, no. 2017, pp.1-15.
https://search.emarefa.net/detail/BIM-1174816
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1174816