Ischemic preconditioning protects cardiomyocytes against ischemic injury by inducing GRP78.
Ischemic preconditioning (IP) conferred by brief ischemia-reperfusion induces resistance to cell injury due to the following lethal ischemia. This study aimed to elucidate whether 78-kDa glucose-regulated protein (GRP78), a main ER molecular chaperone, contributes to IP-mediated protection against ischemic myocardial injury. In a rat coronary artery occlusion model, the GRP78 protein level increased to 210% of the sham level by early IP with three cycles of 4-min ischemia and 4-min reperfusion. The IP reduced infarct size in subsequent lethal ischemia. In primary cardiomyocytes, the simulated IP procedure, incubation in oxygen-glucose deprivation (OGD) medium, also increased the GRP78 expression and suppressed the cell death caused by lethal ischemia. Transfection of grp78 antisense oligonucleotide attenuated the IP-mediated resistance to ischemia. This study showed for the first time that early IP up-regulates myocardial GRP78. It was suggested that GRP78 induced by early IP contributes to protect cardiomyocytes against ischemic injury.
Shintani-Ishida
Kaori
K
Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan. kaori@m.u-tokyo.ac.jp
Nakajima
Makoto
M
Uemura
Koichi
K
Yoshida
Ken-ichi
K
D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D023421:Models, Animal; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014162:Transfection
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D016376:Oligonucleotides, Antisense; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D005947:Glucose; D010100:Oxygen