Related Experiment Video

Updated: Mar 5, 2026

A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
07:39

A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals

Published on: June 25, 2018

7.8K

The stress-response molecule NR4A1 resists ROS-induced pancreatic β-cells apoptosis via WT1

Chen Zong1, Dandan Qin1, Cong Yu1

  • 1Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, Shandong, China.

Cellular Signalling
|March 27, 2017
PubMed

Insights

NR4A1 protein protects pancreatic beta cells from oxidative stress induced by hydrogen peroxide (H2O2). Overexpression of NR4A1 enhances beta cell survival by upregulating WT1 expression, crucial for preventing apoptosis.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Molecular Biology

Background:

  • Pancreatic beta cells are vulnerable to endoplasmic reticulum (ER) stress and reactive oxygen species (ROS)-associated oxidative stress.
  • Previous studies confirmed NR4A1's protective role against ER stress-induced apoptosis in beta cells.
  • The protective function of NR4A1 against ROS-associated oxidative stress remained uninvestigated.

Purpose of the Study:

  • To investigate the role of NR4A1 in protecting pancreatic beta cells against ROS-associated oxidative stress.
  • To elucidate the underlying molecular mechanisms of NR4A1-mediated protection.

Main Methods:

  • NR4A1 protein expression analysis in MIN6 cells treated with H2O2.
  • Overexpression of NR4A1 in MIN6 cells and isolated mouse islets.
  • Assessment of apoptosis and oxidative stress markers (8-hydroxy-2'-deoxyguanosine).
  • Analysis of Caspase 3 activation, WT1, and SOD1 expression.
  • Investigation of NR4A1 binding to the WT1 promoter using chromatin immunoprecipitation assays.

Main Results:

  • NR4A1 expression increased in MIN6 cells upon H2O2 treatment.
  • NR4A1 overexpression conferred resistance to H2O2-induced apoptosis in MIN6 cells and isolated islets.
  • NR4A1 knockout mice exhibited higher oxidative stress and apoptosis rates in islets.
  • NR4A1 overexpression reduced Caspase 3 activation and increased WT1 and SOD1 expression.
  • NR4A1 directly binds to the WT1 promoter, enhancing its transactivation.

Conclusions:

  • NR4A1 plays a significant protective role against ROS-mediated oxidative stress in pancreatic beta cells.
  • NR4A1 confers resistance to H2O2-induced apoptosis, partly through the upregulation of WT1 expression.
  • NR4A1's interaction with the WT1 promoter is a key mechanism in its cytoprotective function.
Keywords:
ApoptosisH(2)O(2)NR4A1Pancreatic β-cellsWT1

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

15.1K
Isolated Pancreatic Islet Treatment and Apoptosis Measurement09:36

Isolated Pancreatic Islet Treatment and Apoptosis Measurement

Published on: May 2, 2025

985

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.0K
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...
10.8K
Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
478
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K