Effect of endothelin on sodium/hydrogen exchanger activity of human monocytes and atherosclerosis-related functions.
The objective of this article is to investigate the influence of endothelin-1 (ET-1) on human monocyte Na(+)/H(+) exchanger (NHE) activity and on the atherosclerosis-related monocyte functions. ET-1 caused an increase in pHi and in (22)Na influx of monocytes. A reversal of ET-1 effect on pHi was observed in the presence of the NHE1 inhibitor, cariporide. In addition, the activation of NHE1 by ET-1 was mediated via protein kinase C (PKC), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and NADPH oxidase. Also, a link between ET-1 and nitric oxide (NO) was observed. Furthermore, after ET-1 treatment, an increase of the adhesive capacity, the migration ability on laminin and CD36 expression of monocytes, was observed; using cariporide this increase was abolished. Our results showed that ET-1 induces a signaling pathway with the involvement of PKC, MAPK, PI3K, and NADPH oxidase where NHE1 plays a key role. ET-1 also plays a significant role in atherosclerosis-related functions of human monocytes, via NHE1 activation.
Koliakos
George
G
Laboratory of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. koliakos@med.auth.gr.
Befani
Christina
C
Paletas
Konstantinos
K
Kaloyianni
Martha
M
D000328:Adult; D050197:Atherosclerosis / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D027682:Cation Transport Proteins; D019332:Endothelin-1; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers