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The effect of stress withdrawal on gene expression and certain biochemical and cell biological properties of peroxide-conditioned cell lines

Department of Ophthalmology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA

² Correspondence: Department of Ophthalmology, Columbia University, 630 W. 168th St., New York, NY 10032, USA. E-mail as42{at}columbia.edu

Maturity onset cataract is a disease that afflicts >25% of the U.S. population over 65. Oxidative stress is believed to be a major factor in the development of this disease and peroxides are suspected to be prominent stressing agents. To elucidate mechanisms involved in the protection of cells against oxidative stress, immortal murine lens epithelial cells (TN4-1) have been conditioned to survive lethal concentrations of either tertiary butyl hydroperoxide, TBOOH (a lipid peroxide prototype) (T cells), or H₂O₂ (H cells). It was found that T cells survived exposure to H₂O₂ but H cells were killed by TBOOH. In this communication, biological characteristics of the T cells are reported. It is shown that the T cell’s ability to survive TBOOH is lost if the cells are grown in the absence of this peroxide (denoted as T^- cells). By comparing the differential gene expression of 12,422 genes and ESTs from T and T^- and the unconditioned control cells, 16 genes were found that may account for the loss of resistance to TBOOH. They include 5 glutathione-S-transferases, superoxide dismutase 1, zeta crystallin, a NADPH quinone reductase, as well as genes involved in detoxifying aldehydes, controlling iron metabolism, and degrading toxic lipoproteins.—Ma, W., Li, D., Sun, F., Kleiman, N. J., Spector, A. The effect of stress withdrawal on the gene expression and certain biochemical and cell biological properties of peroxide-conditioned cell lines

Key Words: microarrays • hydrogen peroxide • tertiary butyl hydroperoxide • GSH-S-transferase • catalase • cataract