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Open AccessArticle

Cytosolic 5′-Nucleotidase II Is a Sensor of Energy Charge and Oxidative Stress: A Possible Function as Metabolic Regulator

1
Unità di Biochimica, Dipartimento di Biologia, Università di Pisa, Via San Zeno 51, 56127 Pisa, Italy
2
Unità di Fisiologia Generale, Dipartimento di Biologia, Università di Pisa, Via San Zeno 31, 56127 Pisa, Italy
3
Department of Medicine, University of California, La Jolla, San Diego, CA 92093-0671, USA
4
Istituto di Neuroscienze, CNR, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy
5
Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR 5286, Faculté Rockefeller, 8 Avenue Rockefeller, 69008 Lyon, France
*
Author to whom correspondence should be addressed.
Cells 2021, 10(1), 182; https://doi.org/10.3390/cells10010182
Received: 2 December 2020 / Revised: 8 January 2021 / Accepted: 15 January 2021 / Published: 18 January 2021
(This article belongs to the Special Issue Purine Signaling and Metabolism in Tumors)
Cytosolic 5′-nucleotidase II (NT5C2) is a highly regulated enzyme involved in the maintenance of intracellular purine and the pyrimidine compound pool. It dephosphorylates mainly IMP and GMP but is also active on AMP. This enzyme is highly expressed in tumors, and its activity correlates with a high rate of proliferation. In this paper, we show that the recombinant purified NT5C2, in the presence of a physiological concentration of the inhibitor inorganic phosphate, is very sensitive to changes in the adenylate energy charge, especially from 0.4 to 0.9. The enzyme appears to be very sensitive to pro-oxidant conditions; in this regard, the possible involvement of a disulphide bridge (C175-C547) was investigated by using a C547A mutant NT5C2. Two cultured cell models were used to further assess the sensitivity of the enzyme to oxidative stress conditions. NT5C2, differently from other enzyme activities, was inactivated and not rescued by dithiothreitol in a astrocytoma cell line (ADF) incubated with hydrogen peroxide. The incubation of a human lung carcinoma cell line (A549) with 2-deoxyglucose lowered the cell energy charge and impaired the interaction of NT5C2 with the ice protease-activating factor (IPAF), a protein involved in innate immunity and inflammation. View Full-Text
Keywords: Cytosolic 5′-nucleotidase II; NT5C2; energy charge; oxidative stress; AMPK; ADF; A549; IPAF Cytosolic 5′-nucleotidase II; NT5C2; energy charge; oxidative stress; AMPK; ADF; A549; IPAF
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MDPI and ACS Style

Pesi, R.; Allegrini, S.; Balestri, F.; Garcia-Gil, M.; Cividini, F.; Colombaioni, L.; Jordheim, L.P.; Camici, M.; Tozzi, M.G. Cytosolic 5′-Nucleotidase II Is a Sensor of Energy Charge and Oxidative Stress: A Possible Function as Metabolic Regulator. Cells 2021, 10, 182. https://doi.org/10.3390/cells10010182

AMA Style

Pesi R, Allegrini S, Balestri F, Garcia-Gil M, Cividini F, Colombaioni L, Jordheim LP, Camici M, Tozzi MG. Cytosolic 5′-Nucleotidase II Is a Sensor of Energy Charge and Oxidative Stress: A Possible Function as Metabolic Regulator. Cells. 2021; 10(1):182. https://doi.org/10.3390/cells10010182

Chicago/Turabian Style

Pesi, Rossana; Allegrini, Simone; Balestri, Francesco; Garcia-Gil, Mercedes; Cividini, Federico; Colombaioni, Laura; Jordheim, Lars P.; Camici, Marcella; Tozzi, Maria G. 2021. "Cytosolic 5′-Nucleotidase II Is a Sensor of Energy Charge and Oxidative Stress: A Possible Function as Metabolic Regulator" Cells 10, no. 1: 182. https://doi.org/10.3390/cells10010182

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