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Lipid peroxidation-mediated cytotoxicity and DNA damage in U937 cells.
Biochimie. 2002 Dec; 84(12):1199-205.B

Abstract

Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. In the present study, we evaluated lipid peroxidation-mediated cytotoxicity and oxidative DNA damage in U937 cells. Upon exposure of U937 cells to tert-butylhydroperoxide (t-BOOH) and 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), which induce lipid peroxidation in membranes, the cells exhibited a reduction in viability and an increase in the endogenous production of reactive oxygen species (ROS), as measured by the oxidation of 2',7'-dichlorodihydrofluorescein. In addition, a significant decrease in the intracellular GSH level and the activities of major antioxidant enzymes were observed. We also observed lipid peroxidation-mediated oxidative DNA damage, reflected by an increase in 8-OH-dG level and loss of the ability of DNA to renature. When the cells were pretreated with the antioxidant N-acetylcysteine (NAC) or the spin trap alpha-phenyl-N-t-butylnitrone (PBN), lipid peroxidation-mediated cytotoxicity in U937 cells was protected. This effect seems to be due to the ability of NAC and PBN to reduce ROS generation induced by lipid peroxidation. These results suggest that lipid peroxidation resulted in a pro-oxidant condition of U937 cells by the depletion of GSH and inactivation of antioxidant enzymes, which consequently leads to a decrease in survival and oxidative damage to DNA. The results indicate that the peroxidation of lipid is probably one of the important intermediary events in oxidative stress-induced cellular damage.

Authors+Show Affiliations

Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12628296

Citation

Park, Ji Eun, et al. "Lipid Peroxidation-mediated Cytotoxicity and DNA Damage in U937 Cells." Biochimie, vol. 84, no. 12, 2002, pp. 1199-205.
Park JE, Yang JH, Yoon SJ, et al. Lipid peroxidation-mediated cytotoxicity and DNA damage in U937 cells. Biochimie. 2002;84(12):1199-205.
Park, J. E., Yang, J. H., Yoon, S. J., Lee, J. H., Yang, E. S., & Park, J. W. (2002). Lipid peroxidation-mediated cytotoxicity and DNA damage in U937 cells. Biochimie, 84(12), 1199-205.
Park JE, et al. Lipid Peroxidation-mediated Cytotoxicity and DNA Damage in U937 Cells. Biochimie. 2002;84(12):1199-205. PubMed PMID: 12628296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipid peroxidation-mediated cytotoxicity and DNA damage in U937 cells. AU - Park,Ji Eun, AU - Yang,Joon-Hyuck, AU - Yoon,Seon Joo, AU - Lee,Jin-Hyup, AU - Yang,Eun Sun, AU - Park,Jeen-Woo, PY - 2003/3/12/pubmed PY - 2004/1/7/medline PY - 2003/3/12/entrez SP - 1199 EP - 205 JF - Biochimie JO - Biochimie VL - 84 IS - 12 N2 - Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. In the present study, we evaluated lipid peroxidation-mediated cytotoxicity and oxidative DNA damage in U937 cells. Upon exposure of U937 cells to tert-butylhydroperoxide (t-BOOH) and 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), which induce lipid peroxidation in membranes, the cells exhibited a reduction in viability and an increase in the endogenous production of reactive oxygen species (ROS), as measured by the oxidation of 2',7'-dichlorodihydrofluorescein. In addition, a significant decrease in the intracellular GSH level and the activities of major antioxidant enzymes were observed. We also observed lipid peroxidation-mediated oxidative DNA damage, reflected by an increase in 8-OH-dG level and loss of the ability of DNA to renature. When the cells were pretreated with the antioxidant N-acetylcysteine (NAC) or the spin trap alpha-phenyl-N-t-butylnitrone (PBN), lipid peroxidation-mediated cytotoxicity in U937 cells was protected. This effect seems to be due to the ability of NAC and PBN to reduce ROS generation induced by lipid peroxidation. These results suggest that lipid peroxidation resulted in a pro-oxidant condition of U937 cells by the depletion of GSH and inactivation of antioxidant enzymes, which consequently leads to a decrease in survival and oxidative damage to DNA. The results indicate that the peroxidation of lipid is probably one of the important intermediary events in oxidative stress-induced cellular damage. SN - 0300-9084 UR - https://www.unboundmedicine.com/medline/citation/12628296/Lipid_peroxidation_mediated_cytotoxicity_and_DNA_damage_in_U937_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300908402000391 DB - PRIME DP - Unbound Medicine ER -