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- W3162584322 abstract "Leucine-rich repeat kinase 2 (LRRK2) has been implicated in the pathophysiology of Parkinson's disease. A variety of cells express LRRK2 including neurons and dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity. Most recently, LRRK2 has been shown to up-regulate Na+/Ca2+-exchanger activity in DCs. The elimination of Ca2+ by Na+/Ca2+-exchangers requires maintenance of the Na+ gradient by the Na+/K+-ATPase. The present study thus explored whether LRRK2 impacts on Na+/K+-ATPase expression and function. To this end DCs were isolated from gene-targeted mice lacking lrrk2 (lrrk2-/-) and their wild-type littermates (lrrk2+/+). Na+/K+-ATPase activity was estimated from K+ induced, ouabain sensitive, current determined by whole cell patch clamp. Na+/K+-ATPase α1 subunit transcript and protein levels were determined by RT-PCR and flow cytometry. As a result, the K+ induced current was significantly smaller in lrrk2-/- than in lrrk2+/+DCs and was completely abolished by ouabain (100 µM) in both genotypes. The K+ induced, ouabain sensitive, current was in lrrk2+/+ DCs significantly blunted by the LRRK2 inhibitor GSK2578215A (1 µM, 24 hours). The Na+/K+-ATPase α1 subunit transcript and protein levels were significantly lower in lrrk2-/- than in Lrrk2+/+DCs and significantly decreased by the LRRK2 inhibitor GSK2578215A (1 µM, 24 hours). In conclusion, LRRK2 is a powerful regulator of Na+/K+-ATPase expression and activity." @default.
- W3162584322 created "2021-05-24" @default.
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- W3162584322 date "2015-01-01" @default.
- W3162584322 modified "2023-09-23" @default.
- W3162584322 title "Leucine-rich repeat kinase 2-sensitive Na+/K+ ATPase activity in dendritic cells" @default.
- W3162584322 hasPublicationYear "2015" @default.
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