Abstract

Aquaporins (AQPs) facilitate water and glycerol permeation through membranes and a few isoforms can also permeate H2O2 (peroxiporins). Increased H2O2 levels misbalance cell redox reactions and may induce tumorigenesis. Recently, we evaluated H2O2 permeability of mammalian AQPs individually expressed in yeast and reported the ability of the rat AQP5-transformed yeast strain to conduct H2O2. Sequence alignment of human and rat AQP5 isoforms show a sequence identity of 91%. Therefore, we next investigated H2O2 permeation by human AQP5 and related cell resistance to oxidative stress. The results indicate that, similarly to AQP3, and AQP8, human AQP5 also permeates H2O2 and importantly, improves cell resistance under oxidative stress. In addition, the effect of anti-oxidant compounds on hAQP5-dependent H2O2 accumulation and cell growth was examined. Curcumin and naringenin enhanced cell resistance in AQP5-transformed yeast cells and anti-proliferative properties known for these compounds were attenuated in yeast cells expressing human AQP5. These data suggest an important role of AQP5 in oxidative stress resistance and point to a novel mechanism explaining AQP5 involvement in cancer.

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