Related Experiment Video

Updated: May 8, 2026

Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo
10:35

Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo

Published on: April 6, 2022

Glucose availability is a decisive factor for Nrf2-mediated gene expression

Elke H Heiss1, Daniel Schachner, Kristin Zimmermann

  • 1Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.

Redox Biology
|September 12, 2013
PubMed

Insights

Nuclear factor-erythroid 2-related factor 2 (Nrf2) activation increases glucose metabolism via the pentose phosphate pathway, which is crucial for its antioxidant defense functions. This highlights a direct link between cellular metabolism and detoxification pathways.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Metabolism

Background:

  • Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular defense against oxidative and xenobiotic stress.
  • Nrf2 also influences genes involved in lipid and glucose metabolism, but the connection between these roles is unclear in non-malignant cells.

Purpose of the Study:

  • To investigate whether cytoprotective and metabolic responses mediated by Nrf2 are connected or separable in non-malignant cells.
  • To elucidate the role of glucose metabolism in Nrf2-mediated cellular defense.

Main Methods:

  • Activation of Nrf2 using the small molecule sulforaphane or by knocking out its inhibitor, Keap1.
  • Analysis of cellular glucose uptake and metabolism, specifically focusing on the pentose phosphate pathway and NADPH production.
  • Interference with glucose supply and pentose phosphate pathway function.

Main Results:

  • Nrf2 activation led to increased cellular glucose uptake and a preference for metabolism through the pentose phosphate pathway, enhancing NADPH production.
  • Impairing glucose supply or pentose phosphate pathway function compromised Nrf2-mediated detoxification of reactive oxygen species and antioxidant gene expression.
  • Nrf2-initiated expression of antioxidant proteins like glutathione reductase and heme-oxygenase-1 was dependent on the pentose phosphate pathway.

Conclusions:

  • Nrf2-dependent protection against oxidative stress is reliant on an intact pentose phosphate pathway.
  • There is significant crosstalk between metabolism and detoxification at the gene expression level in mammalian cells, mediated by Nrf2.
Keywords:
3BP, 3-bromopyruvateATP, adenosine triphosphateDCF, dichloroflouresceinDHEA, dehydroandrostendioneDMSO, dimethylsulfoxideG6PD, glucose 6-phosphate dehydrogenaseGR, glutathione reductaseGlucose addictionGlut1, glucose transporter 1HO-1, heme oxygenase-1Keap1, Kelch-like ECH-associated protein1MEF, mouse embryonic fibroblastsMaf, small masculoaponeurotic fibrosarcomaNADP, nicotine adenine dinucleotide phosphateNQO1, NAD(P)H:quinone oxidoreductase 1Nrf2Nrf2, nuclear factor-erythroid 2-related factor 2OXPHOS, oxidative phosphorylationPBS, phosphate buffered salinePPP, pentose phosphate pathwayROS detoxificationROS, reactive oxygen speciesSFN, sulforaphaneWT, wild typectrl, control

More Related Videos

Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
Glucose Transporters01:27

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Constitutive and Regulated Gene Expression01:27

Constitutive and Regulated Gene Expression

Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...