Cardioprotective effects of 3-phosphoinositide-dependent protein kinase-1 on hypoxic injury in cultured neonatal rat cardiomyocytes and myocardium in a rat myocardial infarct model.
3-Phosphoinositide-dependent protein kinase-1 (PDK1) is involved in numerous cellular responses. In this study, we investigated the protective effects of PDK1 gene expression against hypoxic conditions in cultured rat CMCs (rCMCs) and in a rat myocardial infarction (MI) model using the lentiviral vector (LeV) system. LeV-PDK1 transfer effectively reduced the apoptotic cell death caused by hypoxic injury as compared to LeV-GFP transfer in rCMCs the expression of survival proteins increased in the LeV-PDK1 group, whereas apoptosis signaling decreased in the rCMCs and in infarcted hearts treated with LeV-PDK1. LeV-PDK1 transfer also reduced apoptosis and infarct size and attenuated myocardial wall thinning and ventricular remodeling in a rat MI model. These findings suggest that PDK1 has a protective role in the injured ischemic myocardium via overexpression of the cell survival pathway in CMCs. Hence PDK1 can be used as a treatment strategy for myocardial salvage inin hypoxic injury.
Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea.
Tae-Jin
TJ
Shim
Jang-Whan
JW
Bae
Yeon-Jung
YJ
Kim
Dae Joong
DJ
Kim
Kyung-Kuk
KK
Hwang
Dong-Woon
DW
Kim
Myeong-Chan
MC
Cho
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016086:Lentivirus / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578579:Pdpk1 protein, rat; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3