Specific aquaporins facilitate Nox-produced hydrogen peroxide transport through plasma membrane in leukaemia cells.
In the last decade, the generation and the role of reactive oxygen species (ROS), particularly hydrogen peroxide, in cell signalling transduction pathways have been intensively studied, and it is now clear that an increase of ROS level affects cellular growth and proliferation pathways related to cancer development. Hydrogen peroxide (H2O2) has been long thought to permeate biological membranes by simple diffusion since recent evidence challenged this notion disclosing the role of aquaporin water channels (AQP) in mediating H2O2 transport across plasma membranes. We previously demonstrated that NAD(P)H oxidase (Nox)-generated ROS sustain glucose uptake and cellular proliferation in leukaemia cells. The aim of this study was to assess whether specific AQP isoforms can channel Nox-produced H2O2 across the plasma membrane of leukaemia cells affecting downstream pathways linked to cell proliferation. In this work, we demonstrate that AQP inhibition caused a decrease in intracellular ROS accumulation in leukaemia cells both when H2O2 was produced by Nox enzymes and when it was exogenously added. Furthermore, AQP8 overexpression or silencing resulted to modulate VEGF capacity of triggering an H2O2 intracellular level increase or decrease, respectively. Finally, we report that AQP8 is capable of increasing H2O2-induced phosphorylation of both PI3K and p38 MAPK and that AQP8 expression affected positively cell proliferation. Taken together, the results here reported indicate that AQP8 is able to modulate H2O2 transport through the plasma membrane affecting redox signalling linked to leukaemia cell proliferation.
Department of Pharmacy and Biotechnology, University of Bologna, Italy. Electronic address: francesco.vieceli2@unibo.it.
Francesco
F
Vieceli Dalla Sega
Department of Pharmacy and Biotechnology, University of Bologna, Italy.
Laura
L
Zambonin
Department of Pharmacy and Biotechnology, University of Bologna, Italy.
Diana
D
Fiorentini
Department for Life Quality Studies, University of Bologna, Italy.
Benedetta
B
Rizzo
Department of Cardiology and Laboratory for Technologies of Advanced Therapies (LTTA Center), University Hospital of Ferrara and Maria Cecilia Hospital, GVM Care&Research, E.S: Health Science Foundation, Cotignola, Italy.
Cristiana
C
Caliceti
Laura
L
Landi
Department for Life Quality Studies, University of Bologna, Italy.
Silvana
S
Hrelia
Department of Pharmacy and Biotechnology, University of Bologna, Italy.
Cecilia
C
Prata
D020346:Aquaporins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D020346:Aquaporins; D017382:Reactive Oxygen Species; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C108330:aquaporin 8; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases
Aquaporin; Hydrogen peroxide; Leukaemia cells; NAD(P)H oxidase; ROS; Redox signalling