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DJ‐1/Park7 Sensitive Na + /H + Exchanger 1 (NHE1) in CD4 + T Cells
Author(s) -
Zhou Yuetao,
Shi Xiaolong,
Chen Hong,
Zhang Shaqiu,
Salker Madhuri S.,
Mack Andreas F.,
Föller Michael,
Mak Tak W.,
Singh Yogesh,
Lang Florian
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25516
Subject(s) - physics , chemistry
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.