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

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Jan 22

PMID 33477638

Citations 3

Authors

Rossana Pesi

Simone Allegrini

Francesco Balestri

Mercedes Garcia-Gil

Federico Cividini

Laura Colombaioni

Lars Petter Jordheim

Marcella Camici

Maria Grazia Tozzi

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Transcriptional and Metabolic Investigation in 5'-Nucleotidase Deficient Cancer Cell Lines.

Cadassou O, Forey P, Machon C, Petrotto E, Chettab K, Tozzi M Cells. 2021; 10(11).

PMID: 34831141 PMC: 8616413. DOI: 10.3390/cells10112918.

Cytosolic 5'-Nucleotidase II Silencing in Lung Tumor Cells Regulates Metabolism through Activation of the p53/AMPK Signaling Pathway.

Pesi R, Allegrini S, Garcia-Gil M, Piazza L, Moschini R, Jordheim L Int J Mol Sci. 2021; 22(13).

PMID: 34209768 PMC: 8268954. DOI: 10.3390/ijms22137004.

Metabolic Aspects of Adenosine Functions in the Brain.

Garcia-Gil M, Camici M, Allegrini S, Pesi R, Tozzi M Front Pharmacol. 2021; 12:672182.

PMID: 34054547 PMC: 8160517. DOI: 10.3389/fphar.2021.672182.

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