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

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Journal of Cellular Physiology

Published online on


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 (pHi) 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. 9999: 1–10, 2017. © 2017 Wiley Periodicals, Inc. Our study described that DJ‐1 deficient CD4+ T cells leads to upregulation of NHE1 and enhanced ROS production, therefore results in increase in NHE1 activity. NHE1 regulation in DJ‐1 deficient CD4+ T cells is dependent on ROS and PTK signaling. Thus, our data first time described that link between DJ‐1 proteins with responses on ROS production and NHE1 functions.