Low-concentration of perifosine surprisingly protects cardiomyocytes from oxygen glucose deprivation.
Biochem Biophys Res Commun
; 469(3): 753-60, 2016 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-26686418
ABSTRACT
Here we found that low-concentration of perifosine, an Akt inhibitor, surprisingly protected cardiomyocytes from oxygen glucose deprivation (OGD)/re-oxygenation. In H9c2 cardiomyocytes, non-cytotoxic perifosine (0.1-0.5 µM) suppressed OGD/re-oxygenation-induced reactive oxygen species (ROS) production, p53 mitochondrial translocation and cyclophilin D complexation, as well as mitochondrial membrane potential (MMP) reduction. Molecularly, perifosine activated AMP-activated kinase (AMPK) signaling to increase intracellular NADPH (nicotinamide adenine dinucleotide phosphate) content in H9c2 cells. On the other hand, AMPK inhibition by AMPKα1 shRNA-knockdown in H9c2 cells significantly reduced perifosine-induced NADPH production, and alleviated perifosine-mediated anti-oxidant and cytoprotective activities against OGD/re-oxygenation. In primary murine cardiomyocytes, perifosine similarly activated AMPK signaling, and offered significant protection against OGD/re-oxygenation, which was largely attenuated with siRNA knockdown of AMPKα1. We demonstrate an unexpected function of perifosine (low-concentration) in protecting cardiomyocytes from OGD/re-oxygenation.
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Base de dados:
MEDLINE
Assunto principal:
Fosforilcolina
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Estresse Oxidativo
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Miócitos Cardíacos
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Glucose
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article