Endoplasmic Reticulum Stress Induced by Toxic Elements—a Review of Recent Developments

  • S. V. S. RanaEmail author


Endoplasmic reticulum of all eukaryotic cells is a membrane-bound organelle. Under electron microscope it appears as parallel arrays of “rough membranes” and a maze of “smooth vesicles” respectively. It performs various functions in cell, i.e., synthesis of proteins to degradation of xenobiotics. Bioaccumulation of drugs/chemicals/xenobiotics in the cytosol can trigger ER stress. It is recognized by the accumulation of unfolded or misfolded proteins in the lumen of ER. Present review summarizes the present status of knowledge on ER stress caused by toxic elements, viz arsenic, cadmium, lead, mercury, copper, chromium, and nickel. While inorganic arsenic may induce various glucose-related proteins, i.e., GRP78, GRP94 and CHOP, XBP1, and calpains, cadmium upregulates GRP78. Antioxidants like ascorbic acid, NAC, and Se inhibit the expression of UPR. Exposure to lead also changes ER stress related genes, i.e., GRP 78, GRP 94, ATF4, and ATF6. Mercury too upregulates these genes. Nickel, a carcinogenic element upregulates the expression of Bak, cytochrome C, caspase-3, caspase-9, caspase-12, and GADD 153. Much is not known on ER stress caused by nanoparticles. The review describes inter-organelle association between mitochondria and ER. It also discusses the interdependence between oxidative stress and ER stress. A cross talk amongst different cellular components appears essential to disturb pathways leading to cell death. However, these molecular switches within the signaling network used by toxic elements need to be identified. Nevertheless, ER stress especially caused by toxic elements still remains to be an engaging issue.


Toxic elements Endoplasmic reticulum stress Oxidative stress Unfolded protein response Biomarkers of endoplasmic reticulum stress Cell death 



Endoplasmic reticulum

ER stress

Endoplasmic reticulum stress


Unfolded protein response


Inositol requiring kinase 1


Initiation factor 2 alpha


PKR-like kinase


Activating transcription factor


Binding protein


Glucose-regulated protein 78


ER-associated degradation


Protein disulfide isomerise


Reactive oxygen species


Flavin adenine nucleotide


Endoplasmic reticulum oxidoreduction 1


Arsenic trioxide


Glucose-related protein 94


C/EBP homologous protein


X-box binding protein


Glucose-stimulated insulin secretion


Gap junctional intercellular communication


NADPH oxidase 4


Mixed function oxidase


N-acetyl cysteine





Financial support from Indian Science Congress Association, Kolkata (India), in the form of Ashutosh Mookerjee Fellowship to the author is gratefully acknowledged. The author is also thankful to the Head of the Department of Toxicology, Ch. Charan Singh University, Meerut (India), for extending the technical and administrative support.

Compliance with Ethical Standards

Conflict of Interest

The author declares that there is no conflict of interest.


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Authors and Affiliations

  1. 1.Department of ToxicologyCh. Charan Singh UniversityMeerutIndia

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