Nox-generated ROS modulate glucose uptake in a leukaemic cell line.
The discovery of superoxide-generating enzymes homologues of phagocytic NAD(P)H oxidase, the Nox family, has led to the concept that reactive oxygen species (ROS) are 'intentionally' generated with biological functions in various cell types. In this study, by treating an acute leukaemic cell line with different antioxidants, ROS generation was shown to be crucially involved in the modulation of glucose transport (mediated by Glut1), which is frequently up-regulated in cancer cells. Then, this study tried to elucidate ROS source(s) and mechanisms by which ROS are involved in Glut1 activity regulation. Results prove that Nox2 and Nox4 are the candidates and that phosphorylation processes are important in the regulation of glucose uptake on which cancer cells rely. On the whole, data suggest that both Glut1 and Nox homologues may be considered new potential targets in the treatment of leukaemia.
Prata
Cecilia
C
Department of Biochemistry, University of Bologna, Italy. cecilia.prata@unibo.it
Maraldi
Tullia
T
Fiorentini
Diana
D
Zambonin
Laura
L
Hakim
Gabriele
G
Landi
Laura
L
D000975:Antioxidants / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species
D000975:Antioxidants; D051272:Glucose Transporter Type 1; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; C495677:SLC2A1 protein, human; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D011505:Protein-Tyrosine Kinases; D005947:Glucose