title: NEDD4-1 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis via the PI3K/Akt pathway.
abstract: Activation of the Akt pathway has been shown to protect the heart from ischaemia/reperfusion (I/R) injury. NEDD4-1 has been shown to positively regulate nuclear trafficking of the activated form of Akt. However, the role of NEDD4-1 in cardiac I/R injury remains to be elucidated. In the present study, Lentiviral vectors were constructed to overexpress or knockdown NEDD4-1 in H9c2 cardiomyocytes subjected to I/R injury or ischemic preconditioning (IPC). The results indicated that NEDD4-1 levels were decreased after I/R and increased after IPC in rat heart tissue and in H9c2 cardiomyocytes. Overexpression of NEDD4-1 activated the Akt pathway and regulated apoptosis-related proteins in H9c2 cardiomyocytes, attenuating SI/R-induced cell apoptosis and caspase 3/7 activities. Furthermore, in vivo overexpression of NEDD4-1 attenuated myocardial apoptosis following myocardial I/R. Our results demonstrated that NEDD4-1 protects the myocardium from I/R induced apoptosis by activating PI3K/Akt signaling.
authors.affiliation: Department of Cardiology, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, 201199, China. 18918169120@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, 201199, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, 201199, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, 201199, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, 201199, China.
authors.forename: Dadong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D000075702:Nedd4 Ubiquitin Protein Ligases / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014161:Transduction, Genetic
chemical_list: D011993:Recombinant Fusion Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618484:Nedd4 protein, rat; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt pathway; Apoptosis; Myocardial ischaemia/reperfusion (I/R) injury; NEDD4-1