title: Allantopyrone A activates Keap1-Nrf2 pathway and protects PC12 cells from oxidative stress-induced cell death.
abstract: Keap1-Nrf2 system is known as a sensor of electrophilic compounds, and protects cells from oxidative stress through induction of various antioxidant enzymes. We found by proteomic analysis that allantopyrone A, a metabolite isolated from an endophytic fungus, upregulates the expression of proteins that are regulated by the transcription factor Nrf2. Indeed, allantopyrone A increased the antioxidant enzyme heme oxygenase-1 in PC12 cells. Moreover, it induced localization of Nrf2 in the nucleus. Affinity purification of allantopyrone A-binding protein showed that this compound could bind directly to Keap1. Allantopyrone A suppressed intracellular reactive oxygen species level and cell death induced by H2O2in PC12 cells. These results indicate that allantopyrone A protects PC12 cells from oxidative stress-induced cell death through direct binding with Keap1 and activation of the Keap1-Nrf2 pathway.
authors: The United Graduate School of Agricultural Sciences, Iwate University, Iwate, Japan.
authors: Shota
authors: S
authors: Uesugi
authors: RIKEN Center for Sustainable Resource Science (CSRS), Saitama, Japan.
authors: Makoto
authors: M
authors: Muroi
authors: RIKEN Center for Sustainable Resource Science (CSRS), Saitama, Japan.
authors: Yasumitsu
authors: Y
authors: Kondoh
authors: Department of Food, Life, and Environmental Science, Faculty of Agriculture, Yamagata University, Yamagata, Japan.
authors: Yoshihito
authors: Y
authors: Shiono
authors: RIKEN Center for Sustainable Resource Science (CSRS), Saitama, Japan.
authors: Hiroyuki
authors: H
authors: Osada
authors: The United Graduate School of Agricultural Sciences, Iwate University, Iwate, Japan.
authors: Ken-Ichi
authors: KI
authors: Kimura
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000187:drug effects / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D040901:Proteomics; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D016877:Oxidants; D011753:Pyrones; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; C550113:allantopyrone A; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1