MEMBRANES AND PHOSPHOLIPIDS IN RENAL HYPERPLASIA

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The objective of the proposed research is to elucidate mechanisms which regulate membrane formation, organelle biogenesis, cellular growth and energy metabolism in the kidneys of potassium (K)-depleted rats. Kidneys of K-depleted rats offer an extraordinary mode system for study of organ growth that can be modulated by dietary changes. The induction of lysosome formation in the renal medulla of K-depleted rats provides a unique opportunity to study the factors which regulate lysosome biogenesis and enzyme formation. The sensitivity of mitochondrial oxidative phosphorylation to alterations in dietary K intake permits study of the role of this ion in the regulation of cellular energy production. Using growing tissue from K-depleted rats we plan to characterize the role of K as a modulator of phospholipid and protein precursor uptake and the enzymatic reactions of phospholipid biosynthesis. The kinetics of synthesis and degradation of a specific lysosomal enzyme will be defined by immunoprecipitation analysis and the cellular locus of lysosome formation will be studied during lysosome biogenesis and regression in the renal papilla of K-depleted and K-repleted rats. The role of K and other cations in mitochondrial energy production and in the integration of glycolysis and respiration will be examined in cells in the inner stripe of the renal red medulla which undergo adenomatous hyperplasia during K depletion. Since alterations in K balance occur in many disease states, elucidation of the biochemical and molecular events that are consequences of this disturbance is of basic importance to medicine and disordered biology.