期刊
JOURNAL OF ANTIBIOTICS
卷 70, 期 4, 页码 429-434出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ja.2016.99
关键词
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资金
- UGAS
- Iwate University
- Grants-in-Aid for Scientific Research [15J04501, 17H06412, 16H04910, 17K07783, 26350976, 16H06276] Funding Source: KAKEN
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 H2O2 in 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.
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