Back to Search
Start Over
Nerve growth factor-induced Akt/mTOR activation protects the ischemic heart via restoring autophagic flux and attenuating ubiquitinated protein accumulation.
- Source :
-
Oncotarget [Oncotarget] 2017 Jan 17; Vol. 8 (3), pp. 5400-5413. - Publication Year :
- 2017
-
Abstract
- The dysregulation of autophagy is related to a variety of cardiovascular diseases, such as myocardial ischemia/reperfusion (I/R). Nerve growth factor (NGF) has been shown to have therapeutic potential in ischaemic heart injury. In this study, we demonstrate that NGF administration can accelerate autophagic flux and attenuate protein ubiquitination in myocardial I/R heart. Our results showed that NGF could restored heart function and decreased the apoptosis of cardiomyocytes which induced by myocardial I/R injury. The protective effect of NGF is associated with the inhibition of autophagy related proteins. On another hand, NGF enhances the clearance of ubiquitinated protein and increases the survival of myocardial cell in vivo and in vitro. Additionally, NGF could activate the PI3K/AKT and mTOR signaling pathways. These results suggested that the cardioprotective effect of NGF is related to the restoration of autophagic flux and attenuation of protein ubiquitination via the activation of PI3K/AKT and mTOR pathway.
- Subjects :
- Animals
Apoptosis drug effects
Male
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
TOR Serine-Threonine Kinases metabolism
Ubiquitinated Proteins metabolism
Autophagy drug effects
Myocardial Reperfusion Injury metabolism
Myocardial Reperfusion Injury physiopathology
Nerve Growth Factor pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 8
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 28036273
- Full Text :
- https://doi.org/10.18632/oncotarget.14284