Studies on the response of phospholipase A(2) to the deficiency of vitamin E and selenium in rat
Abstract
Three questions concerning the cellular responses to oxidative stress in mammalian systems were addressed. The first concerned the effect of altered vitamin E and selenium status on phospholipase A$\sb2$ activity in rat tissues. Long-Evans hooded rats were fed a purified diet for six weeks with or without the addition of vitamin E and selenium in a 2 x 2 factorial design. Deficiency of both vitamin E and selenium profoundly enhanced the calcium-independent phospholipase A$\sb2$ activity in lung and spleen, and to a lesser extent in liver. This response did not occur in the tissues of single nutrient-deficient rats. Calcium-dependent phospholipase A$\sb2$ activity was only slightly affected by the dietary treatments. Inhibitor studies suggest that this activated calcium-independent phospholipase A$\sb2$ is a member of a new group in the phospholipase A$\sb2$ family. The second question was concerned with the time frame of the response of calcium-independent phospholipase A$\sb2$ to vitamin E and selenium deficiency. Time course studies were conducted with Long-Evans hooded rats maintained on either +E, +Se or $-$E, $-$Se diets. In rats consuming the diets deficient in both vitamin E and selenium, the calcium-independent phospholipase A$\sb2$ activity of lung, spleen, and liver increased initially between four and six weeks and increased even further at seven weeks. The initial enhancement could be reversed by partial repletion with vitamin E and selenium. This bi-phasic response to the deficiency occurred one week after indicators of vitamin E and selenium status had reached minimum levels. The final question addressed the uniqueness of the enhanced calcium-independent phospholipase A$\sb2$ in rat lung and liver cytosol through partial purification of the activity. The results obtained from hydrophobic interaction chromatography of lung cytosolic samples of rats consuming diets for four through seven weeks indicated that two distinct forms of calcium-independent phospholipase A$\sb2$ responded to the dietary deficiency of vitamin E and selenium. Additionally, substrate preference toward oxidized phospholipids suggests that these calcium-independent phospholipase A$\sb2$ may play a significant role in the cellular repair mechanism for oxidative damage.
Degree
Ph.D.
Advisors
Burgess, Purdue University.
Subject Area
Nutrition|Pharmacology
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