| First Author | Hosseinzadeh Z | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 41117 | PubMed ID | 28120865 |
| Mgi Jnum | J:275127 | Mgi Id | MGI:6296144 |
| Doi | 10.1038/srep41117 | Citation | Hosseinzadeh Z, et al. (2017) Leucine-Rich Repeat Kinase 2 (Lrrk2)-Sensitive Na(+)/K(+) ATPase Activity in Dendritic Cells. Sci Rep 7:41117 |
| abstractText | Leucine-rich repeat kinase 2 (Lrrk2) has been implicated in the pathophysiology of Parkinson's disease. Lrrk2 is expressed in diverse cells including neurons and dendritic cells (DCs). In DCs Lrrk2 was shown to up-regulate Na(+)/Ca(2+)-exchanger activity. The elimination of Ca(2+) by Na(+)/Ca(2+) -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 alpha1 subunit transcript and protein levels were determined by RT-qPCR 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 muM) in both genotypes. The K(+) induced, ouabain sensitive, current in Lrrk2(+/+) DCs was significantly blunted by Lrrk2 inhibitor GSK2578215A (1 muM, 24 hours). The Na(+)/K(+) -ATPase alpha1 subunit transcript and protein levels were significantly lower in Lrrk2(-/-) than in Lrrk2(+/+) DCs and significantly decreased by Lrrk2 inhibitor GSK2578215A (1 muM, 24 hours). In conclusion, Lrrk2 is a powerful regulator of Na(+)/K(+) -ATPase expression and activity in dendritic cells. |
