It is known that an increase in the intracellular level of reactive oxygen species (ROS), in particolar hydrogen peroxide (H2O2) is able to affect signalling pathways regulating proliferation and cancer development. H2O2 has been long thought to freely permeate across biological membranes, but recently, new evidence demonstrated that membrane H2O2-permeability is limited and that specific acquaporin (AQP) isoforms are able to funnel H2O2 across membranes. Data here reported show that AQP inhibition cause a decrease in intracellular H2O2 accumulation in leukaemia cells. Furthermore, AQP8 overexpression or silencing by means of siRNA resulted in the modulation of VRGF ability of triggering H2O2 intracellular level increase or decrease, respectively. Finally, we show that AQP8-facilitated H2O2 transport is able to increase cell proliferation through a mechanism dependent on PI3K and p38MAPK. In summary, our findings indicate that AQP8 is able to modulate H2O2 transport through the plasma membrane affecting redox signalling linked to leukaemia cell proliferation. Therefore, the development of new drugs targeting specific AQP isoforms might be and interesting novel anti-cancer strategy.

AQP8 facilitates Nox-produced hydrogen peroxide transport in leukaemia cells

VIECELI DALLA SEGA, FRANCESCO;ZAMBONIN, LAURA;FIORENTINI, DIANA;RIZZO, BENEDETTA;PRATA, CECILIA;HRELIA, SILVANA
2014

Abstract

It is known that an increase in the intracellular level of reactive oxygen species (ROS), in particolar hydrogen peroxide (H2O2) is able to affect signalling pathways regulating proliferation and cancer development. H2O2 has been long thought to freely permeate across biological membranes, but recently, new evidence demonstrated that membrane H2O2-permeability is limited and that specific acquaporin (AQP) isoforms are able to funnel H2O2 across membranes. Data here reported show that AQP inhibition cause a decrease in intracellular H2O2 accumulation in leukaemia cells. Furthermore, AQP8 overexpression or silencing by means of siRNA resulted in the modulation of VRGF ability of triggering H2O2 intracellular level increase or decrease, respectively. Finally, we show that AQP8-facilitated H2O2 transport is able to increase cell proliferation through a mechanism dependent on PI3K and p38MAPK. In summary, our findings indicate that AQP8 is able to modulate H2O2 transport through the plasma membrane affecting redox signalling linked to leukaemia cell proliferation. Therefore, the development of new drugs targeting specific AQP isoforms might be and interesting novel anti-cancer strategy.
2014
Proceedings XIII FISV Congress
85
85
F. Vieceli Dalla Sega; L. Zambonin; D Fiorentini; B. Rizzo; C. Prata; S. Hrelia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/359522
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