Related Experiment Video

Updated: Jan 29, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.9K

Nrf2⁻ARE Signaling Acts as Master Pathway for the Cellular Antioxidant Activity of Fisetin

Huihui Zhang1, Wan Zheng2, Xiangling Feng3

  • 1Xiangya School of Public Health, Central South University, Changsha 410128, China. zhanghuihui182@foxmail.com.

Molecules (Basel, Switzerland)
|February 21, 2019
PubMed

Insights

Fisetin enhances cellular antioxidant activity by stabilizing the Nrf2 protein, promoting its nuclear translocation and upregulating antioxidant gene expression. This occurs through inhibiting Nrf2 degradation at the post-transcriptional level.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Pharmacology

Background:

  • Fisetin, a dietary flavonoid, exhibits antioxidant properties.
  • The precise molecular mechanisms underlying fisetin's cellular antioxidant activity remain unclear.
  • Investigating fisetin's impact on key cellular signaling pathways is crucial.

Purpose of the Study:

  • To elucidate the mechanism by which fisetin exerts its cellular antioxidant effects.
  • To investigate the influence of fisetin on the nuclear factor, erythroid 2-like 2 (Nrf2) signaling pathway.
  • To explore fisetin's role in regulating antioxidant response element (ARE) transactivation in HepG2 cells.

Main Methods:

  • HepG2 cells were treated with fisetin.
  • mRNA and protein expression of antioxidant genes (HO-1, GCLC, GCLM, NQO1) were analyzed.
  • Nrf2 nuclear accumulation was assessed via immunofluorescence and Western blotting.
  • ARE-regulated transactivation was measured using dual-luciferase reporter gene assays.
  • Protein stability and ubiquitination of Nrf2 were evaluated using cycloheximide and MG132 treatments.

Main Results:

  • Fisetin upregulated mRNA expression of HO-1, GCLC, GCLM, and NQO1, and induced HO-1 protein.
  • Nuclear accumulation of Nrf2 and enhanced ARE-regulated transactivation were observed.
  • Fisetin increased Nrf2 protein levels and decreased Keap1 protein levels.
  • Fisetin prolonged Nrf2 half-life and reduced Nrf2 ubiquitination, indicating inhibited degradation.
  • Fisetin did not significantly affect Nrf2 mRNA expression.

Conclusions:

  • Fisetin promotes Nrf2 nuclear translocation and upregulates downstream antioxidant gene expression.
  • Fisetin inhibits Nrf2 degradation at the post-transcriptional level, thereby enhancing its stability.
  • These findings elucidate the molecular mechanism of fisetin's cellular antioxidant activity via the Nrf2 pathway.
Keywords:
HO-1Nrf2–ARE pathwayfisetinoxidative stress

More Related Videos

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.7K
Visualization of Cellular Electrical Activity in Zebrafish Early Embryos and Tumors08:55

Visualization of Cellular Electrical Activity in Zebrafish Early Embryos and Tumors

Published on: April 25, 2018

9.3K

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.5K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.3K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.8K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.4K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.6K