Abstract
Endothelin-1 (ET-1) (1-100 nM) decreases the activity of Na,K-ATPase, a key enzyme responsible for aqueous humor formation, in transformed human non-pigmented ciliary epithelial (HNPE) cells. The present study sought to determine if ET-1 alters the expression of the catalytically active alpha subunit of Na,K-ATPase in HNPE cells and identify mechanisms underlying these effects. We report that acute (15 and 30 min) treatment with ET-1 results in an increase in mRNA expression of the α1 subunit of Na,K-ATPase. Similar to ET-1's effects, ouabain (100 μM), a selective inhibitor of Na,K-ATPase, and monensin (10 μM), a sodium ionophore, also increased Na,K-ATPase expression in HNPE cells. The increase in Na,K-ATPase expression by short-term treatment with ouabain and monensin was dependent on their ability to elevate intracellular sodium concentrations. However, acute ET-1 treatment mediated increase in Na,K-ATPase expression was independent of changes in intracellular sodium. A prolonged (24 hr) ET-1 treatment results in an increase in both mRNA and protein levels of the α1 subunit of Na,K-ATPase. These observations suggest that ET-1 could play a homeostatic role in modulating aqueous humor formation by having differential effects on the activity and expression of Na,K-ATPase by the ciliary epithelium in the eye.
| Original language | English |
|---|---|
| Pages (from-to) | 465-481 |
| Number of pages | 17 |
| Journal | Journal of Ocular Pharmacology and Therapeutics |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| State | Published - 1 Jan 2003 |
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Regulation of Na,K-ATPase Expression by Endothelin-1 in Transformed Human Ciliary Non-Pigmented Epithelial (HNPE) Cells. / Krishnamoorthy, Raghu; Prasanna, Ganesh; Dauphin, Rachel; Hulet, Christina; Agarwal, Neeraj; Yorio, Thomas.
In: Journal of Ocular Pharmacology and Therapeutics, Vol. 19, No. 5, 01.01.2003, p. 465-481.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Regulation of Na,K-ATPase Expression by Endothelin-1 in Transformed Human Ciliary Non-Pigmented Epithelial (HNPE) Cells
AU - Krishnamoorthy, Raghu
AU - Prasanna, Ganesh
AU - Dauphin, Rachel
AU - Hulet, Christina
AU - Agarwal, Neeraj
AU - Yorio, Thomas
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Endothelin-1 (ET-1) (1-100 nM) decreases the activity of Na,K-ATPase, a key enzyme responsible for aqueous humor formation, in transformed human non-pigmented ciliary epithelial (HNPE) cells. The present study sought to determine if ET-1 alters the expression of the catalytically active alpha subunit of Na,K-ATPase in HNPE cells and identify mechanisms underlying these effects. We report that acute (15 and 30 min) treatment with ET-1 results in an increase in mRNA expression of the α1 subunit of Na,K-ATPase. Similar to ET-1's effects, ouabain (100 μM), a selective inhibitor of Na,K-ATPase, and monensin (10 μM), a sodium ionophore, also increased Na,K-ATPase expression in HNPE cells. The increase in Na,K-ATPase expression by short-term treatment with ouabain and monensin was dependent on their ability to elevate intracellular sodium concentrations. However, acute ET-1 treatment mediated increase in Na,K-ATPase expression was independent of changes in intracellular sodium. A prolonged (24 hr) ET-1 treatment results in an increase in both mRNA and protein levels of the α1 subunit of Na,K-ATPase. These observations suggest that ET-1 could play a homeostatic role in modulating aqueous humor formation by having differential effects on the activity and expression of Na,K-ATPase by the ciliary epithelium in the eye.
AB - Endothelin-1 (ET-1) (1-100 nM) decreases the activity of Na,K-ATPase, a key enzyme responsible for aqueous humor formation, in transformed human non-pigmented ciliary epithelial (HNPE) cells. The present study sought to determine if ET-1 alters the expression of the catalytically active alpha subunit of Na,K-ATPase in HNPE cells and identify mechanisms underlying these effects. We report that acute (15 and 30 min) treatment with ET-1 results in an increase in mRNA expression of the α1 subunit of Na,K-ATPase. Similar to ET-1's effects, ouabain (100 μM), a selective inhibitor of Na,K-ATPase, and monensin (10 μM), a sodium ionophore, also increased Na,K-ATPase expression in HNPE cells. The increase in Na,K-ATPase expression by short-term treatment with ouabain and monensin was dependent on their ability to elevate intracellular sodium concentrations. However, acute ET-1 treatment mediated increase in Na,K-ATPase expression was independent of changes in intracellular sodium. A prolonged (24 hr) ET-1 treatment results in an increase in both mRNA and protein levels of the α1 subunit of Na,K-ATPase. These observations suggest that ET-1 could play a homeostatic role in modulating aqueous humor formation by having differential effects on the activity and expression of Na,K-ATPase by the ciliary epithelium in the eye.
UR - http://www.scopus.com/inward/record.url?scp=0142244526&partnerID=8YFLogxK
U2 - 10.1089/108076803322473024
DO - 10.1089/108076803322473024
M3 - Article
VL - 19
SP - 465
EP - 481
JO - Journal of Ocular Pharmacology and Therapeutics
JF - Journal of Ocular Pharmacology and Therapeutics
SN - 1080-7683
IS - 5
ER -