Related Experiment Video

Updated: Aug 23, 2026

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

Manganese superoxide dismutase is induced by endoplasmic reticulum stress through IRE1-mediated nuclear factor

Masayuki Kaneko1, Tomoko Takahashi, Yoshifumi Niinuma

  • 1Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

Biological & Pharmaceutical Bulletin
|August 12, 2004
PubMed

Insights

Endoplasmic reticulum (ER) stress increases manganese superoxide dismutase (MnSOD) expression. This occurs via IRE1-mediated activation of NF-kappaB and AP-1, highlighting a novel ER stress signaling pathway.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Manganese superoxide dismutase (MnSOD) is a key mitochondrial antioxidant enzyme.
  • MnSOD is typically induced by stimuli activating nuclear factor-kappaB (NF-kappaB) and Activator Protein-1 (AP-1).
  • Endoplasmic reticulum (ER) stress is a cellular response to various insults affecting protein homeostasis.

Purpose of the Study:

  • To investigate the effect of ER stress on MnSOD expression in HeLa cells.
  • To elucidate the signaling pathways involved in ER stress-induced MnSOD upregulation.

Main Methods:

  • HeLa cells were treated with agents inducing ER stress.
  • mRNA and protein levels of MnSOD were quantified.
  • Expression of ER stress-related transcription factors (ATF6, IRE1, XBP1) was manipulated.
  • NF-kappaB and AP-1 activation were assessed using a dominant-negative IRE1 mutant.

Main Results:

  • Agents inducing ER stress significantly increased MnSOD mRNA and protein levels.
  • Overexpression of ATF6, IRE1, or XBP1 did not affect MnSOD levels.
  • ER stress induced NF-kappaB and AP-1 activation, which was blocked by a dominant-negative IRE1 mutant.
  • ER stress-induced MnSOD expression was significantly reduced by the dominant-negative IRE1 mutant.

Conclusions:

  • ER stress upregulates MnSOD expression in HeLa cells.
  • This upregulation is mediated through the IRE1 signaling pathway.
  • IRE1 activation leads to NF-kappaB and AP-1 activation, ultimately controlling MnSOD expression during ER stress.

More Related Videos

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication10:12

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

Published on: June 14, 2024

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...
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...
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...