ER chaperone GRP78 regulates autophagy by modulation of p53 localization.
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 ofGRP78, leads to nuclear localization of p53 and induces autophagy while Rotenone down regulatesGRP78, causes cytoplasmic localization of p53 and inhibits autophagy. Therefore, it may be concluded thatGRP78affects p53 localization which in turn regulates autophagy.
Department of Biosciences, Faculty of Applied Sciences, Integral University, Lucknow, Uttar Pradesh, India.
Mohd
M
Kamil
Department of Biosciences, Faculty of Applied Sciences, Integral University, Lucknow, Uttar Pradesh, India.
Ejazul
E
Haque
Department of Biosciences, Faculty of Applied Sciences, Integral University, Lucknow, Uttar Pradesh, India.
Safia
S
Irfan
Department of Biosciences, Faculty of Applied Sciences, Integral University, Lucknow, Uttar Pradesh, India.
Saba
S
Sheikh
Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, Uttar Pradesh, India.
Adria
A
Hasan
Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology,CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
Aamir
A
Nazir
Department of Biosciences, Faculty of Applied Sciences, Integral University, Lucknow, Uttar Pradesh, India.
Mohtashim
M
Lohani
Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, Uttar Pradesh, India, smir@iul.ac.in.
Snober S
SS
Mir
D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010278:Parathion / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
D002843:Chromatin; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D012402:Rotenone; D010278:Parathion