Related Experiment Video

Updated: Mar 20, 2026

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

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

15.2K

Endoplasmic reticulum stress eIF2α-ATF4 pathway-mediated cyclooxygenase-2 induction regulates cadmium-induced

B Luo1, Y Lin1, S Jiang1

  • 1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.

Cell Death & Disease
|June 3, 2016
PubMed

Insights

Cadmium exposure causes kidney damage by inducing autophagy. This study reveals that endoplasmic reticulum stress activates the eIF2α-ATF4 pathway, leading to cyclooxygenase-2 (COX-2) overexpression, which drives cadmium-induced kidney autophagy and injury.

Area of Science:

  • Toxicology
  • Cell Biology
  • Molecular Biology

Background:

  • Cadmium (Cd) is a nephrotoxic heavy metal.
  • Autophagy is implicated in cadmium-induced kidney injury, but mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying cadmium-induced kidney injury and autophagy.
  • To investigate the role of cyclooxygenase-2 (COX-2) and endoplasmic reticulum (ER) stress in this process.

Main Methods:

  • In vivo and in vitro studies using kidney tissues and cultured cells.
  • Induction of ER stress and measurement of autophagy markers.
  • Inhibition of COX-2 and ER stress pathways using celecoxib, 4-phenylbutyrate, and RNA interference (RNAi).
  • Assessment of ATF4 activation and nuclear translocation.

Main Results:

  • Cadmium induced kidney damage, dysfunction, and autophagy.
  • Cadmium activated the ER stress eIF2α-ATF4 pathway, leading to COX-2 overexpression.
  • Inhibition of COX-2 or ER stress attenuated cadmium-induced autophagy.
  • ATF4 activation was necessary for COX-2 overexpression.

Conclusions:

  • A novel mechanism links ER stress, the eIF2α-ATF4 pathway, and COX-2 overexpression to cadmium-induced kidney autophagy and injury.
  • COX-2 represents a potential therapeutic target for mitigating cadmium nephrotoxicity.

More Related Videos

Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions06:32

Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions

Published on: June 13, 2025

613

Related Concept Videos

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...
6.7K
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...
7.7K
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...
3.2K
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...
5.4K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
3.0K
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
845