Oxidative stress and mitochondrial adaptive shift during pituitary tumoral growth

M. EUGENIA SABATINO; EZEQUIEL GRONDONA; LILIANA DEL V. SOSA; BETHANIA MONGI BRAGATO; LUCIA CARREÑO; VIRGINIA JUAREZ; RODRIGO A. DA SILVA; ALINE REMOR; LUCILA DE BORTOLI; ROBERTA DE PAULA MARTINS; PABLO A. PÉREZ; JUAN PABLO PETITI; SILVINA GUTIÉRREZ; ALICIA I. TORRES; ALEXANDRA LATINI; ANA L. DE PAUL

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2018 p. 41 - 55

0891-5849

The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellularmetabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumourgrowth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumourdevelopment are not well understood. Pituitary tumours present endocrine neoplastic benign growth which, inprevious reports, we had shown that in addition to increased proliferation, these tumours were also characterizedby cellular senescence signs with no indication of apoptosis. Here, we show clear evidence of oxidativestress in pituitary cells, accompanied by bigger and round mitochondria during tumour development, associatedwith augmented biogenesis and an increased fusion process. An activation of the Nrf2 stress response pathwaytogether with the attenuation of the oxidative damage signs occurring during tumour development were alsoobserved which will probably provide survival advantages to the pituitary cells. These neoplasms also presenteda progressive increase in lactate production, suggesting a metabolic shift towards glycolysis metabolism. Thesefindings might imply an oxidative stress state that could impact on the pathogenesis of pituitary tumours. Thesedata may also reflect that pituitary cells can modulate their metabolism to adapt to different energy requirementsand signalling events in a pathophysiological situation to obtain protection from damage and enhancetheir survival chances. Thus, we suggest that mitochondria function, oxidative stress or damage might play acritical role in pituitary tumour progression.