ROLE OF ORNITHINE DECARBOXYLASE IN ENTEROCYTE MITOCHONDRIAL-FUNCTION AND INTEGRITY

We examined the role of ornithine decarboxylase (ODC) and polyamine bi osynthesis in regulating mitochondrial function and integrity along th e crypt-villus axis in male Sprague-Dawley rats. Isolated villus tip e nterocytes from control rats demonstrated a greater cellular capacity for glucose oxidation than crypt enterocytes. Mitochondrial enzyme act ivities were similar along the crypt-villus axis. The role of ODC was assessed by treating experimental rats with the irreversible ODC inhib itor ol-difluoromethylornithine (DFMO) for 24 h. Animals receiving DFM O demonstrated a decreased CO2 production from [2-C-14]pyruvate along the entire crypt-villus axis coupled with an increase in lactate produ ction in the upper cell populations. CO2 production from [C-14]glucose and total ATP levels were not affected by DFMO treatment. Ultrastruct ural examination revealed localized mitochondrial swelling and burstin g only in enterocytes corresponding to the population of cells newly e merged from the crypt during DFMO treatment. In DFMO-treated animals, 2 mu M spermine completely prevented the structural mitochondrial inju ry and restored the metabolic crypt-villus gradient. These results sug gest that as enterocytes migrate from the crypt up the villus, mitocho ndrial function increases to handle the increased metabolic demands pl aced on the cell by nutrient absorption. ODC activity and polyamines a re necessary for this increased mitochondrial function and have a role in the maintenance of mitochondrial integrity in maturing enterocytes migrating from the crypt onto the villus.