MITOCHONDRIAL DAMAGE AND METABOLIC COMPENSATORY MECHANISMS INDUCED BY HYPEROXIA IN U-937 CELL LINE.

Experimental hyperoxia represents a suitable in vitro model to study some pathogenic mechanisms related to oxidative stress. Moreover, it allows the investigation of the molecular pathophysiology underlying oxygen therapy and oxygen toxicity. In this study, we adopted a modified experimental set up to accomplish a model of moderate hyperoxia (50% O2, 96 hours culture) in order to induce oxidative stress in the human leukemia cell line U-937. Spectrophotometric measurements of mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media, determination of antioxidant enzyme activities, cell proliferation and differentiation assays were performed. Data showed that moderate hyperoxia in this myeloid cell line causes: i) an intriguing alteration of mitochondrial activities at the level of succinate dehydrogenase and succinate-cytochrome c reductase; ii) an induction of metabolic compensatory adaptations with a significant shift to glycolysis; iii) an induction of different antioxidant enzyme activities; iv) a significant cell growth inhibition; v) no significant apoptosis. This work permitted to better characterize the mitochondrial damage induced by hyperoxia. In particular, data showed a large increase of succinate cytochrome c reductase activity that could be a fundamental pathogenic mechanism at the basis of oxygen toxicity.