Glutathionylation of the Aquaporin-2 water channel: a novel post-translational modification modulated by the oxidative stress. [Membrane Biology]

August 11th, 2014 by Tamma, G., Ranieri, M., Di Mise, A., Centrone, M., Svelto, M., Valenti, G.

Aquaporin-2 (AQP2) is the vasopressin regulated water channel that controls renal water reabsorption and urine concentration. AQP2 undergoes different regulated posttranslational modifications, including phosphorylation and ubiquitylation, which are fundamental for controlling AQP2 cellular localization, stability and function. The relationship between AQP2 and S-glutathionylation is of potential interest because reactive oxygen species (ROS), produced under renal failure or nephrotoxic drugs, may influence renal function as well as the expression and the activity of different transporters and channels, including aquaporins. Here, we show, for the first time, that AQP2 is subjected to S-glutathionylation in kidney and in HEK-293 cells stably expressing AQP2. S-Glutathionylation is a redox-dependent posttranslational modification controlling several signal transduction pathways and displaying an acute effect on free cytosolic calcium concentration. Interestingly, we found that, in fresh kidney slices, the increased AQP2 S-glutathionylation correlated with tBHP-induced ROS generation. Moreover, we also found that cells expressing wild-type Calcium Sensing Receptor (hCaSR-wt) and its gain of function (hCaSR-R990G; hCaSR-N124K) had a significant decrease in AQP2 S-glutathionylation secondary to reduced ROS levels and reduced basal intracellular calcium concentration compared to mock cells. Together, these new findings provide fundamental insight into cell biological aspects of AQP2 function and may be relevant to better understand and explain pathological states characterized by an oxidative stress and AQP2-dependent water reabsorption disturbs.
  • Posted in Journal of Biological Chemistry, Publications
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