Molecular pharmacology
-
Molecular pharmacology · Oct 2009
Resveratrol protects mitochondria against oxidative stress through AMP-activated protein kinase-mediated glycogen synthase kinase-3beta inhibition downstream of poly(ADP-ribose)polymerase-LKB1 pathway.
Arachidonic acid (AA, a proinflammatory fatty acid) in combination with iron promotes excess reactive oxygen species (ROS) production and exerts a deleterious effect on mitochondria. We have shown previously that activation of AMP-activated protein kinase (AMPK) protects hepatocytes from AA + iron-induced apoptosis. Resveratrol, a polyphenol in grapes, has beneficial effects mediated through SIRT1, LKB1, and AMPK. ⋯ Furthermore, this LKB1-dependent mitochondrial protection resulted from resveratrol's poly(ADP-ribose)polymerase activation, but not SIRT1 activation, as supported by the experiment using 3-aminobenzamide, a poly(ADP-ribose)polymerase inhibitor. Other polyphenols, such as apigenin, genistein, and daidzein, did not activate AMPK or protect mitochondria against AA + iron. Thus, resveratrol protects cells from AA + iron-induced ROS production and mitochondrial dysfunction through AMPK-mediated inhibitory phosphorylation of GSK3beta downstream of poly(ADP-ribose)polymerase-LKB1 pathway.