Live-cell imaging Unveils stimulus-specific dynamics of Nrf2 activation in UV-exposed melanoma cells: Implications for antioxidant compound screening
Issued Date
2024-02-01
Resource Type
ISSN
08915849
eISSN
18734596
Scopus ID
2-s2.0-85179814769
Pubmed ID
38092271
Journal Title
Free Radical Biology and Medicine
Volume
211
Start Page
1
End Page
11
Rights Holder(s)
SCOPUS
Bibliographic Citation
Free Radical Biology and Medicine Vol.211 (2024) , 1-11
Suggested Citation
Htut N.W., Onkoksoong T., Saelim M., Kueanjinda P., Sampattavanich S., Panich U. Live-cell imaging Unveils stimulus-specific dynamics of Nrf2 activation in UV-exposed melanoma cells: Implications for antioxidant compound screening. Free Radical Biology and Medicine Vol.211 (2024) , 1-11. 11. doi:10.1016/j.freeradbiomed.2023.12.007 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95825
Title
Live-cell imaging Unveils stimulus-specific dynamics of Nrf2 activation in UV-exposed melanoma cells: Implications for antioxidant compound screening
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Corresponding Author(s)
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Abstract
The transcription factor Nuclear factor e2-related factor 2 (Nrf2) is pivotal in orchestrating cellular antioxidant defense mechanisms, particularly in skin cells exposed to ultraviolet (UV) radiation and electrophilic phytochemicals. To comprehensively investigate Nrf2's role in maintaining cellular redox equilibrium following UV-induced stress, we engineered a novel Nrf2 fusion-based reporter system for real-time, live-cell quantification of Nrf2 activity in human melanoma cells. Utilizing live quantitative imaging, we dissected the kinetic profiles of Nrf2 activation in response to an array of stimuli, including UVA and UVB radiation, as well as a broad spectrum of phytochemicals including ferulic acid, gallic acid, hispidulin, p-coumaric acid, quercetin, resveratrol, tannic acid, and vanillic acid as well as well-known Nrf2 inducers, tert-butylhydroquinone (tBHQ) and sulforaphane (SFN). Intriguingly, we observed distinct dynamical patterns of Nrf2 activity contingent on the specific stimuli applied. Sustained activation of Nrf2 was empirically correlated with the increased antioxidant response element (ARE) activity. Our findings demonstrate the nuanced impact of different phenolic compounds on Nrf2 activity and the utility of our Nrf2-CTΔ16-YFP reporter in characterizing the dynamics of Nrf2 translocation in response to diverse stimuli. In summary, our innovative reporter system not only revealed compounds capable of modulating UVA-induced Nrf2 activity but also showcased its utility as a robust tool for future antioxidant compound screening efforts.