AQP8 modulates hydrogen peroxide signalling in leukaemia cells

Aquaporins (AQP) are channels that transport water and other small solutes across plasma membranes. In human, 13 different AQP isoforms have been discovered and three of them (AQP1, AQP3 and AQP8) have recently been reported to channel hydrogen peroxide (H2O2). Interestingly, the three AQP isoforms that possess the capacity of channel H2O2 are also widely expressed in blood cells. It is known that H2O2 can act as a messenger in cell signalling pathways and that an increase in intracellular ROS level supports pro-survival pathways contributing to cancer development. We previously demonstrated that H2O2 produced by NAD(P)H oxidases (Nox) promotes cellular proliferation in leukaemia cells. The aim of this work 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 the present study we report that specific AQP isoforms (AQP8 and AQP3, in a lesser extent) constitute a possible way through which Nox-derived H2O2 can enter leukaemia cells. Moreover, we demonstrate that AQP8 overexpression is able to enhance intracellular H2O2 accumulation induced by VEGF. Furthermore, we show that AQP8 is capable of amplifying phosphorylation triggered by H2O2 of both PI3K and p38 MAPK. In summary, results here reported indicate that AQP8 is able to modulate H2O2 transport through plasma membrane contributing to the aberrant proliferation of leukaemia cells.