Mitochondrial damage and metabolic compensatory mechanisms induced by hyperoxia in the 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 toxicity. In this study, a modified experimental set up was adopted to accomplish a model of moderate hyperoxia (50% O(2), 96 h culture) 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, and cell proliferation and differentiation assays were performed. The data showed that moderate hyperoxia in this myeloid cell line causes: i) intriguing alterations in the mitochondrial activities at the levels of succinate dehydrogenase and succinate-cytochrome c reductase; ii) induction of metabolic compensatory adaptations, with significant shift to glycolysis; iii) induction of different antioxidant enzyme activities; iv) significant cell growth inhibition and v) no significant apoptosis. This work will permit better characterization the mitochondrial damage induced by hyperoxia. In particular, the data showed a large increase in the succinate cytochrome c reductase activity, which could be a fundamental pathogenic mechanism at the basis of oxygen toxicity.
Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy. r.scatena@rm.unicatt.it
Roberto
R
Scatena
Irene
I
Messana
Giuseppe Ettore
GE
Martorana
Maria Luisa
ML
Gozzo
Silvio
S
Lippa
Alessandro
A
Maccaglia
Patrizia
P
Bottoni
Federica
F
Vincenzoni
Giuseppina
G
Nocca
Massimo
M
Castagnola
Bruno
B
Giardina
D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress
D000975:Antioxidants; D015415:Biomarkers; D005947:Glucose