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Serum deprivation-induced HepG2 cell death is potentiated by CYP2E1.
Free Radic Biol Med. 2006 Jan 01; 40(1):63-74.FR

Abstract

Induction of oxidative stress plays a key role in serum deprivation-induced apoptosis. CYP2E1 plays an important role in toxicity of many chemicals and ethanol and produces oxidant stress. We investigated whether CYP2E1 expression can sensitize HepG2 cells to toxicity as a consequence of serum deprivation. The models used were HepG2 E47 cells that express human CYP2E1, and C34 HepG2 cells which do not express CYP2E1. E47 cells showed greater growth inhibition and enhanced cell death after serum deprivation, as compared to the C34 cells. DNA ladder and flow cytometry assays indicated that apoptosis occurred at earlier times after serum deprivation in E47 than C34 cells. Serum withdrawal-induced E47 cell death could be rescued by antioxidants, the mitochondrial permeability transition inhibitor cyclosporine A, z-DEVD-fmk, and a CYP2E1 inhibitor 4-methylpyrazole. Increased production of reactive oxygen species (ROS) and lipid peroxidation occurred in E47 cells after serum deprivation, and there was a corresponding decline in the E47 cell mitochondrial membrane potential and reduced glutathione (GSH) levels. We propose that the mechanism of this serum withdrawal plus CYP2E1 toxicity involves increased production of intracellular ROS, lipid peroxidation, and decline of GSH levels, which results in mitochondrial membrane damage and loss of membrane potential, followed by apoptosis. Potentiation of serum deprivation-induced cell death by CYP2E1 may contribute to the sensitivity of the liver to alcohol-induced ischemia and growth factor deprivation.

Authors+Show Affiliations

Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L. Place, New York, NY 10029, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16337880

Citation

Zhuge, Jian, and Arthur I. Cederbaum. "Serum Deprivation-induced HepG2 Cell Death Is Potentiated By CYP2E1." Free Radical Biology & Medicine, vol. 40, no. 1, 2006, pp. 63-74.
Zhuge J, Cederbaum AI. Serum deprivation-induced HepG2 cell death is potentiated by CYP2E1. Free Radic Biol Med. 2006;40(1):63-74.
Zhuge, J., & Cederbaum, A. I. (2006). Serum deprivation-induced HepG2 cell death is potentiated by CYP2E1. Free Radical Biology & Medicine, 40(1), 63-74.
Zhuge J, Cederbaum AI. Serum Deprivation-induced HepG2 Cell Death Is Potentiated By CYP2E1. Free Radic Biol Med. 2006 Jan 1;40(1):63-74. PubMed PMID: 16337880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum deprivation-induced HepG2 cell death is potentiated by CYP2E1. AU - Zhuge,Jian, AU - Cederbaum,Arthur I, Y1 - 2005/09/02/ PY - 2005/05/18/received PY - 2005/08/08/revised PY - 2005/08/12/accepted PY - 2005/12/13/pubmed PY - 2006/3/17/medline PY - 2005/12/13/entrez SP - 63 EP - 74 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 40 IS - 1 N2 - Induction of oxidative stress plays a key role in serum deprivation-induced apoptosis. CYP2E1 plays an important role in toxicity of many chemicals and ethanol and produces oxidant stress. We investigated whether CYP2E1 expression can sensitize HepG2 cells to toxicity as a consequence of serum deprivation. The models used were HepG2 E47 cells that express human CYP2E1, and C34 HepG2 cells which do not express CYP2E1. E47 cells showed greater growth inhibition and enhanced cell death after serum deprivation, as compared to the C34 cells. DNA ladder and flow cytometry assays indicated that apoptosis occurred at earlier times after serum deprivation in E47 than C34 cells. Serum withdrawal-induced E47 cell death could be rescued by antioxidants, the mitochondrial permeability transition inhibitor cyclosporine A, z-DEVD-fmk, and a CYP2E1 inhibitor 4-methylpyrazole. Increased production of reactive oxygen species (ROS) and lipid peroxidation occurred in E47 cells after serum deprivation, and there was a corresponding decline in the E47 cell mitochondrial membrane potential and reduced glutathione (GSH) levels. We propose that the mechanism of this serum withdrawal plus CYP2E1 toxicity involves increased production of intracellular ROS, lipid peroxidation, and decline of GSH levels, which results in mitochondrial membrane damage and loss of membrane potential, followed by apoptosis. Potentiation of serum deprivation-induced cell death by CYP2E1 may contribute to the sensitivity of the liver to alcohol-induced ischemia and growth factor deprivation. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/16337880/Serum_deprivation_induced_HepG2_cell_death_is_potentiated_by_CYP2E1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(05)00456-9 DB - PRIME DP - Unbound Medicine ER -