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

作者：Zhou, Yuetao; Shi, Xiaolong; Chen, Hong; Zhang, Shaqiu; Salker, Madhuri S.; Mack, Andreas F.; Foeller, Michael; Mak, Tak W.; Singh, Yogesh^*; Lang, Florian^*

来源：Journal of Cellular Physiology, 2017, 232(11): 3050-3059.

DOI：10.1002/jcp.25516

• PARKINSONS-DISEASE
• DENDRITIC CELLS
• DJ-1
• EXPRESSION
• PLASTICITY
• PROTEIN
• HEART
• GENE
• PROGESTERONE
• HOMEOSTASIS

DJ-I /Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-I 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 I (NHEI). ROS formation in CD4(+) T cells plays a decisive role in regulating inflammatory responses. In the present study, we explored whether DJ-I is expressed in CD4(+) T cells, and affects ROS production as well as NHEI in those cells. To this end, DJ-I and NHEI transcript, and protein levels were quantified by qRT-PCR and Western blotting, respectively, intracellular pH (pH;) utilizing bis-(2carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from realkalinization after an ammonium pulse, and ROS production utilizing dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ-I was expressed in CD4(+) T cells. ROS formation, NHEI transcript levels, NHE I protein, and NHE activity were higher in CD4(+-)T cells from DJ-I 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-I deficient CD4(+) T cells, and blunted the difference between DJ-I-/- and DJ-I (+/+) CD4(+) T cells, an observation pointing to a role of ROS in the up-regulation of NHEI in DJ-I CD4(+) T cells. In conclusion, DJ-I is a powerful regulator of ROS production as well as NHEI expression and activity in CD4(+) T cells. 2016 Wiley Periodicals, Inc.

• 出版日期2017-11
• 单位四川农业大学