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

Abstract

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 ) 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.

Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cells

“…NHE1 expression and Na + /H + exchanger activity are highly sensitive to oxidative stress [17, 21]. Na + /H + exchanger activity in turn impacts on NADPH oxidase activation and generation of reactive oxygen species [17].…”

Role of DJ-1 in Immune and Inflammatory Diseases

“…It is likely triggered by the elevated proliferation of DJ-1 deficient CD3 + T cells and enhanced migration in response to stromal cell-derived factor-1 via overexpression of chemokine receptor 4 (13,85). In addition, a new relationship between the DJ-1-ROS-Na + /H + exchanger 1 (NHE1) revealed that DJ-1-deficient CD4 + T cells upregulated the expression and activity of NHE1, which may have resulted from enhanced ROS generation (86). In turn, NHE1 activity can impair ROS production (86).…”

“…In addition, a new relationship between the DJ-1-ROS-Na + /H + exchanger 1 (NHE1) revealed that DJ-1-deficient CD4 + T cells upregulated the expression and activity of NHE1, which may have resulted from enhanced ROS generation (86). In turn, NHE1 activity can impair ROS production (86). In this respect, lack of DJ-1 promotes neointima formation since NHE1 contributes to cell migration (87).…”

DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs)

“…The authors suggested that the DJ1-C57 model effectively recapitulates the early stages of PD and allow study of the preclinical aspects of neurodegeneration 14 . Our own studies with DJ-1 −/− mice also suggested that DJ-1 protein is involved in the regulation of adaptive immune CD4 + T cells and their development and functions by modifying of sodium hydrogen exchanger 1 (NHE1) and ROS formation 15,16 . One should keep in mind that different DJ-1 −/− mice lines with different background could be more or less prone to develop neurodegeneration and in additive to genetic changes additional environmental and unknown factors may play a crucial role for the disease development in DJ-1 −/− mice.…”