IMR Press / FBE / Volume 9 / Issue 1 / DOI: 10.2741/E785

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

ER chaperone GRP78 regulates autophagy by modulation of p53 localization

Show Less
1 Department of Biosciences, Faculty of Applied Sciences, Integral University, Lucknow, Uttar Pradesh, India
2 Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, Uttar Pradesh, India
3 Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

*Author to whom correspondence should be addressed.

Academic Editor: Saheem Ahmad

Front. Biosci. (Elite Ed) 2017, 9(1), 54–66; https://doi.org/10.2741/E785
Published: 1 January 2017
(This article belongs to the Special Issue Biotechnological advancements in free radical biology and medicine)
Abstract

GRP78 (glucose regulated protein 78) is a major Endoplasmic Reticulum (ER) chaperone that plays a pivotal role in normal ER functioning. Its increased expression also works as an indicator of ER stress. Its anti-apoptotic and pro-autophagic activity makes it an intriguing target to study the relationship between GRP78 and p53, which is also a major regulator of apoptosis and autophagy. Here, we studied the effect of Rotenone and Parathion on human lung cancer cells (A549 cell line) specifically with respect to ER stress and its association with different cell death pathways. In our study, we observed that both compounds increase reactive oxygen species (ROS) generation, down regulate mitochondrial membrane potential (MMP) and affect DNA integrity. Our results indicate that Parathion causes ER stress, up regulates the expression of GRP78, leads to nuclear localization of p53 and induces autophagy while Rotenone down regulates GRP78, causes cytoplasmic localization of p53 and inhibits autophagy. Therefore, it may be concluded that GRP78 affects p53 localization which in turn regulates autophagy.

Keywords
Endoplasmic Reticulum Stress
GRP78
Rotenone
Parathion
Autophagy
Apoptosis
p53 Localization
Share
Back to top