DJ-1/Park7 Sensitive Na⁺ /H⁺ Exchanger 1 (NHE1) in CD4⁺ T Cells

DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na⁺ /H⁺ exchanger 1 (NHE1). ROS formation in CD4⁺ T cells plays a decisive role in regulating inflammatory responses. In the present study, we explored whether DJ-1 is expressed in CD4⁺ T cells, and affects ROS production as well as NHE1 in those cells. To this end, DJ-1 and NHE1 transcript, and protein levels were quantified by qRT-PCR and Western blotting, respectively, intracellular pH (pH_i ) utilizing bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from realkalinization after an ammonium pulse, and ROS production utilizing 2',7' -dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ-1 was expressed in CD4⁺ T cells. ROS formation, NHE1 transcript levels, NHE1 protein, and NHE activity were higher in CD4⁺ T cells from DJ-1 deficient mice than in CD4⁺ T cells from wild type mice. Antioxidant N-acetyl-cysteine (NAC) and protein tyrosine kinase (PTK) inhibitor staurosporine decreased the NHE activity in DJ-1 deficient CD4⁺ T cells, and blunted the difference between DJ-1^-/- and DJ-1^+/+ CD4⁺ T cells, an observation pointing to a role of ROS in the up-regulation of NHE1 in DJ-1^-/- CD4⁺ T cells. In conclusion, DJ-1 is a powerful regulator of ROS production as well as NHE1 expression and activity in CD4⁺ T cells. J. Cell. Physiol. 232: 3050-3059, 2017. © 2016 Wiley Periodicals, Inc.