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 (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. 232: 3050-3059, 2017. © 2016 Wiley Periodicals, Inc.

• Authors: Yuetao Zhou, Xiaolong Shi, Hong Chen, Shaqiu Zhang, Madhuri S Salker, Andreas F Mack, Michael Föller, Tak W Mak, Yogesh Singh, Florian Lang
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 232 Issue 11 Pg. 3050-3059 (Nov 2017) ISSN: 1097-4652 [Electronic] United States
• PMID: 27509531 (Publication Type: Journal Article)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Antioxidants
• Cation Transport Proteins
• Protein Kinase Inhibitors
• RNA, Messenger
• Reactive Oxygen Species
• Slc9a1 protein, mouse
• Sodium-Hydrogen Exchanger 1
• Sodium-Hydrogen Exchangers
• Protein-Tyrosine Kinases
• PARK7 protein, mouse
• Protein Deglycase DJ-1

Topics

• Animals
• Antioxidants (pharmacology)
• CD4-Positive T-Lymphocytes (drug effects, metabolism)
• Cation Transport Proteins (antagonists & inhibitors, genetics, metabolism)
• Cells, Cultured
• Genotype
• Hydrogen-Ion Concentration
• Mice, Inbred C57BL
• Mice, Knockout
• Phenotype
• Protein Deglycase DJ-1 (deficiency, genetics, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• RNA, Messenger (genetics, metabolism)
• Reactive Oxygen Species (metabolism)
• Sodium-Hydrogen Exchanger 1
• Sodium-Hydrogen Exchangers (antagonists & inhibitors, genetics, metabolism)
• Time Factors
• Up-Regulation