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• W2107101475 abstract "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. This study investigated the potential of resveratrol to protect against the mitochondrial impairment induced by AA + iron and the underlying mechanism for this cytoprotection. Resveratrol treatment inhibited apoptosis, ROS production, and glutathione depletion elicited by AA + iron in HepG2 cells. In addition, resveratrol attenuated superoxide generation in mitochondria and inhibited mitochondrial dysfunction induced by AA + iron. Overall, AMPK activation by resveratrol contributed to cell survival, as supported by the reversal of its restoration of mitochondrial membrane potential by either overexpression of a dominant-negative mutant of AMPKα or compound C treatment. Resveratrol increased inhibitory phosphorylation of glycogen synthase kinase-3β (GSK3β) downstream of AMPK, which contributed to mitochondrial protection and cell survival. Likewise, small interfering RNA knockdown of LKB1, an upstream kinase of AMPK, reduced the ability of resveratrol to protect cells from mitochondrial dysfunction. Furthermore, this LKB1-dependent mitochondrial protection resulted from resveratrol9s 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 GSK3β downstream of poly(ADP-ribose)polymerase-LKB1 pathway." @default.
• W2107101475 created "2016-06-24" @default.
• W2107101475 creator A5084423872 @default.
• W2107101475 creator A5086387142 @default.
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• W2107101475 date "2009-07-20" @default.
• W2107101475 modified "2023-09-26" @default.
• W2107101475 title "Resveratrol Protects Mitochondria against Oxidative Stress through AMP-Activated Protein Kinase-Mediated Glycogen Synthase Kinase-3β Inhibition Downstream of Poly(ADP-ribose)polymerase-LKB1 Pathway" @default.
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• W2107101475 doi "https://doi.org/10.1124/mol.109.058479" @default.
• W2107101475 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19620254" @default.
• W2107101475 hasPublicationYear "2009" @default.
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