+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Decreased protein and mRNA expression of ER stress proteins GRP78 and GRP94 in HepG2 cells over-expressing CYP2E1



Decreased protein and mRNA expression of ER stress proteins GRP78 and GRP94 in HepG2 cells over-expressing CYP2E1



Archives of Biochemistry and Biophysics 447(2): 155-166



CYP2E1 causes oxidative stress mediated cell death; the latter is one mechanism for endoplasmic reticulum (ER) stress in the cell. Unfolded proteins accumulate during ER stress and ER resident proteins GRP78 and GRP94 protect cells against ER dysfunction. We examined the possible role of GRP78 and GRP94 as protective factors against CYP2E1-mediated toxicity in HepG2 cells expressing CYP2E1 (E47 cells). E47 cells expressed high levels of CYP2E1 protein and catalytic activity which is associated with increased ROS generation, lipid peroxidation and the elevated presence of ubiquinated and aggregated proteins as compared to control HepG2 C34 cells which do not express CYP2E1. The mRNA and protein expression of GRP78 and GRP94 were decreased in E47 cells compared to the C34 cells, which may explain the accumulation of ubiquinated and aggregated proteins. Expression of these GRP proteins was induced with the ER stress agent thapsigargin in E47 cells, and E47 cells were more resistant to the toxicity caused by thapsigargin and calcimycin, possibly due to this upregulation and also because of the high expression of GSH and antioxidant enzymes in E47 cells. Antioxidants such as trolox and N-acetylcysteine increased GRP78 and GRP94 levels in the E47 cells, suggesting that CYP2E1- derived oxidant stress was responsible for down regulation of these GRPs in the E47 cells. Thapsigargin mediated toxicity was decreased in cells treated with the antioxidant trolox indicating a role for oxidative stress in this toxicity. These results suggest that CYP2E1 mediated oxidative stress downregulates the expression of GRP proteins in HepG2 cells and oxidative stress is an important mechanism in causing ER dysfunction in these cells.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011925464

Download citation: RISBibTeXText

PMID: 16497268

DOI: 10.1016/j.abb.2006.01.013


Related references

HCV core protein modifies oxidative stress in HepG2 cells expressing CYP2E1. Hepatology 36(4 Part 2): 475A, 2002

Expression of the glucose-regulated proteins (GRP94 and GRP78) in differentiated and undifferentiated mouse embryonic cells and the use of the GRP78 promoter as an expression system in embryonic cells. Differentiation; Research in Biological Diversity 42(3): 153-159, 1990

The effect of astragalus injection on the expression of endoplasmic reticulum stress chaperonin GRP78 and GRP94 mRNA in adriamycin-injured cardiomyocytes with calumenin silencing by shRNA. Zhongguo Ying Yong Sheng Li Xue Za Zhi 32(2): 154-157, 2016

Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1. Journal of Medical Virology 72(2): 230-240, 2004

Inhibition of CYP2E1 leads to decreased advanced glycated end product formation in high glucose treated ADH and CYP2E1 over-expressing VL-17A cells. Biochimica et Biophysica Acta 1830(10): 4407-4416, 2013

Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1. Hepatology 43(1): 144-153, 2006

CYP2E1-mediated oxidative stress induces COL1A2 mRNA in hepatic stellate cells and in a coculture system of HepG2 and stellate cells. Hepatology 30(4 Part 2): 485A, 1999

Decreased functional expression of Grp78 and Grp94 inhibits proliferation and attenuates apoptosis in a human gastric cancer cell line in vitro. Oncology Letters 9(3): 1181-1186, 2015

Decreased ABCB1 mRNA expression induced by atorvastatin results from enhanced mRNA degradation in HepG2 cells. European Journal of Pharmaceutical Sciences 37(3-4): 486-491, 2009

Expression and clinical significance of glucose regulated proteins GRP78 and GRP94 in human colon cancer. Chinese Journal of Cancer Research 22(1): 42-48, 2010

Toxicity of ethanol in HepG2 cells expressing CYP2E1. Alcoholism Clinical & Experimental Research 24(5 Suppl.): 165A, 2000

Suppression of stress proteins, GRP78, GRP94, calreticulin and calnexin in liver endoplasmic reticulum of rat treated with a highly toxic coplanar PCB. Fukuoka Igaku Zasshi 92(5): 201-216, 2001

Expression and clinical significance of glucose regulated proteins GRP78 (BiP) and GRP94 (GP96) in human adenocarcinomas of the esophagus. Bmc Cancer 8: 70, 2008

Protein kinase C signaling as a survival pathway against CYP2E1-derived oxidative stress and toxicity in HepG2 cells. Journal of Pharmacology and Experimental Therapeutics 312(3): 998, 2005

Endoplasmic reticulum stress-inducible protein GRP94 is associated with an Mg2+-dependent serine kinase activity modulated by Ca2+ and GRP78/BiP. Journal of Cellular Physiology 170(2): 115-129, 1997