Role of ornithine decarboxylase in enterocyte mitochondrial function and integrity

Abstract

We examined the role of ornithine decarboxylase (ODC) and polyamine biosynthesis in regulating mitochondrial function and integrity along the crypt-villus axis in male Sprague-Dawley rats. Isolated villus tip enterocytes from control rats demonstrated a greater cellular capacity for glucose oxidation than crypt enterocytes. Mitochondrial enzyme activities were similar along the crypt-villus axis. The role of ODC was assessed by treating experimental rats with the irreversible ODC inhibitor alpha-difluoromethylornithine (DFMO) for 24 h. Animals receiving DFMO demonstrated a decreased CO2 production from [2-(14)C]pyruvate along the entire crypt-villus axis coupled with an increase in lactate production in the upper cell populations. CO2 production from [14C]glucose and total ATP levels were not affected by DFMO treatment. Ultrastructural examination revealed localized mitochondrial swelling and bursting only in enterocytes corresponding to the population of cells newly emerged from the crypt during DFMO treatment. In DFMO-treated animals, 2 microM spermine completely prevented the structural mitochondrial injury and restored the metabolic crypt-villus gradient. These results suggest that as enterocytes migrate from the crypt up the villus, mitochondrial function increases to handle the increased metabolic demands placed on the cell by nutrient absorption. ODC activity and polyamines are 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.