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 H 2 O 2 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.

H2S-Induced Sulfhydration: Biological Function and Detection Methodology

“…Numerous experimental results show that the oxidative stress sensor protein Keap1 and Nrf2 are closely related to the oxidative stress injury and the antioxidant response ( Uesugi et al, 2017 ; Wasik et al, 2017 ). Previous studies suggested that H 2 S played an important role in protecting against oxidative stress by enhancing Nrf2 nuclear translocation and initiating antioxidant response in ischemia-reperfusion injury ( Calvert et al, 2009 ; Guo et al, 2014 ; Shimada et al, 2015 ), diabetes-accelerated atherosclerosis ( Xie et al, 2016 ) and high salt-induced renal injury ( Huang et al, 2016 ).…”