ReferenceID 3820
Activated AMPK boosts the Nrf2/HO-1 signaling axis--A role for the unfolded protein response
Free Radic Biol Med
In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regula
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 3820
- Evidence Id
- 20410
- Core Evidence Id
- 20410
- Source Reference Id
- 925
- Herb2 Reference Id
- HBREF001587
- Subject Paper Key
- HBIN048442_25843659
- Pubmed Id
- 25843659
- Doi
- 10.1016/j.freeradbiomed.2015.03.030
- Paper Title
- Activated AMPK boosts the Nrf2/HO-1 signaling axis--A role for the unfolded protein response
- Paper Abstract
- In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regulators of the cellular redox and energy balance, respectively. Making use of xanthohumol (XN) as an activator of both the AMPK and the Nrf2 signaling pathway we show that AMPK exerts a positive influence on Nrf2/heme oxygenase (HO)-1 signaling in mouse embryonic fibroblasts. Genetic ablation and pharmacological inhibition of AMPK blunts Nrf2-dependent HO-1 expression by XN already at the mRNA level. XN leads to AMPK activation via interference with mitochondrial function and activation of liver kinase B1 as upstream AMPK kinase. The subsequent AMPK-mediated enhancement of the Nrf2/HO-1 response does not depend on inhibition of the mammalian target of rapamycin, inhibition of glycogen synthase kinase 3β, or altered abundance of Nrf2 (total and nuclear). However, reduced endoplasmic reticulum stress was identified and elaborated as a step in the AMPK-augmented Nrf2/HO-1 response. Overall, we shed more light on the hitherto incompletely understood cross talk between the LKB1/AMPK and the Nrf2/HO-1 axis revealing for the first time involvement of the unfolded protein response as an additional player and suggesting tight cooperation between signaling pathways controlling cellular redox, energy, or protein homeostasis.
- Journal
- Free Radic Biol Med
- Publish Year
- 2015
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Activated AMPK boosts the Nrf2/HO-1 signaling axis--A role for the unfolded protein response
- Bilingual Status
- semi_complete