Oxidative stress and the subcellular localization of the telomerase reverse transcriptase (TERT) in papillary thyroid cancer. (15th August 2016)

• Record Type: Journal Article
• Authors: Muzza, Marina; Colombo, Carla; Cirello, Valentina; Perrino, Michela; Vicentini, Leonardo; Fugazzola, Laura
• Is Part Of: Molecular and cellular endocrinology. Volume 431(2016)
• Page Start: 54
• Page End: 61
• Publication Date: 2016-08-15
• Subjects: TERT -- Oxidative stress -- DUOX -- NOX -- Thyroid cancer; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.05.005
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: During hormonogenesis, thyrocytes are physiologically exposed to high levels of oxidative stress (OS) which could either be involved in the pathogenesis of thyroid cancer or exert a cytotoxic effect. We analyzed the oxidative status of papillary thyroid cancer (PTC) both directly, by measuring H2 O2 generation by NADPH oxidases (NOXs), and indirectly, by evaluating the antioxidant activity of glutathione peroxidase (GPX), which neutralizes H2 O2 excess, and the lipid peroxidation (LP). Moreover, we investigated the subcellular localization of telomerase reverse transcriptase (TERT), and the H2 O2 levels in the mitochondria of tumor and normal tissues. The calcium-dependent and independent H2 O2 generation activity was significantly higher in tumors than in normal tissues. The GPX activity was higher in PTCs than in normal tissues, and, consistently, no differences were found in LP levels. Moreover, while TERT nuclear expression was similar in tumor and normal tissues, the mitochondrial localization was significantly higher in tumors. At the mitochondrial level, no differences were found in H2 O2 generation between tumor and normal tissues. In conclusion, present data demonstrate that the intracellular H2 O2 generation by NOXs is significantly higher in PTCs than in normal thyroid tissues. The increased GPX activity found in tumors counteracts the potential cytotoxic effects of high OS exposure. The significantly higher mitochondrial localization of TERT in tumors is consistent with its shuttling from the nucleus upon exposure to high OS. Finally, mitochondrial OS was not significantly different in tumors and normal tissues, supporting the postulated role of mitochondrial TERT in the control of local H2 O2 production. Highlights: The H2 O2 generation activity is significantly higher in tumors than in normal tissues. In thyroid tumors TERT shuttles from the nucleus to the mitochondria. Mitochondrial H2 O2 activity is not significantly different in tumors and normal tissues.