Studies on the glutathione dependent protection of the cell nucleus against lipid peroxidation Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/j67316022

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  • Lipid peroxidation is believed to be an important process in the development of cellular injury. In addition to the degradation of biological membranes, increasing evidence indicates that lipid peroxidation can alter the structure and function of DMA. The present study examines the peroxidation of nuclear membranes and the capacity of glutathione to inhibit this process. Research indicates that glutathione protects isolated rat liver nuclei against both ascorbate and NADPH induced peroxidation. Evidence suggests that a glutathione dependent peroxidase associated with the nuclear membrane is required for this protection. Inhibition and substrate specificity requirements show that this peroxidase is a glutathione transferase. Partially purified nuclear glutathione transferase lipid hydroperoxides. Since lipid hydroperoxides can catalyze the propagation of lipid peroxidation, the reduction of these compounds in biological membranes should contribute to the inhibition of lipid peroxidation. Vitamin E has also been shown to be an effective inhibitor of lipid peroxidation in vitro. In experiments conducted with isolated nuclei supplemented with vitamin E, vitamin E protected against lipid peroxidation only when vitamin E was present above a certain critical level. If vitamin E levels were below this threshold value, peroxidation was not inhibited. The addition of gluta thione reduced the threshold levels of vitamin E required to protect against lipid peroxidation. These results show that vitamin E and glutathione act synergistically to inhibit nuclear lipid peroxidation. Research has shown that nuclear membranes contain pores which allow the free diffusion of small water soluble metabolites between the nucleus and cytoplasm. Experiments were conducted to determine the levels of glutathione in the nucleus. Rat kidney cell nuclei were isolated by nonaqueous isolation techniques to minimize the loss of glutathione during isolation. Results suggest that with normal cellular glutathione levels, the con centration of glutathione in the nucleus is similar to that found in the cytoplasm. Administration of buthionine sulfoximine to rats reduced cellular glutathione levels in the kidney. However, nuclear glutathione levels were reduced to a much greater extent than cytosolic levels.
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  • description.provenance : Submitted by Katy Davis (kdscannerosu@gmail.com) on 2013-06-14T22:13:55Z No. of bitstreams: 1 TirmensteinMarkA1988.pdf: 1011790 bytes, checksum: 8bb23d338d67fd4dda17001d11bec2f4 (MD5)
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  • description.provenance : Approved for entry into archive by Deborah Campbell(deborah.campbell@oregonstate.edu) on 2013-07-02T21:29:41Z (GMT) No. of bitstreams: 1 TirmensteinMarkA1988.pdf: 1011790 bytes, checksum: 8bb23d338d67fd4dda17001d11bec2f4 (MD5)
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