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Nickel and extracellular acidification inhibit the water permeability of human aquaporin-3 in lung epithelial cells.
KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
2003 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 32, 30037-43 p.Article in journal (Refereed) Published
Abstract [en]

Nickel is a common cause of pneumoconiosis. Here, we show that nickel inactivates aquaporin (AQP)-3, the water channel expressed apically in epithelial cells of human terminal airways. Human AQP3 was transiently transfected into human lung cells, and water permeability was measured in transfected and neighboring untransfected cells. Incubation with NiCl2 rapidly, dose-dependently, and reversibly decreased water permeability in AQP3-expressing cells. Acidification of the extracellular medium also caused rapid, dose-dependent, and reversible inhibition of AQP3. Sensitivity of AQP3 to nickel was lower at alkaline pH than at neutral and acidic pH. Cells transfected with human AQP4 and AQP5, which are also expressed in airway epithelia, were insensitive to nickel and extracellular acidification. Zinc and cadmium, other common causes of pneumoconiosis, had no effect on the water permeability of AQP3. Three extracellular residues, Trp128, Ser152, and His241, were responsible for the blocking effect of nickel on human AQP3. Ser152 was identified as a common site for nickel and pH sensitivity. His53, Tyr124, and His154 were also involved in regulation of AQP3 by extracellular pH. In addition, the aromatic side chain of His154 was shown to be important for the water permeability of AQP3. Our results imply that nickel and extracellular pH may modulate lung water clearance and that defective water clearance may be an early component of nickel-induced lung disease.

Place, publisher, year, edition, pages
2003. Vol. 278, no 32, 30037-43 p.
National Category
Cell Biology
URN: urn:nbn:se:kth:diva-80469DOI: 10.1074/jbc.M302206200PubMedID: 12773542OAI: diva2:496366
NR 20140805Available from: 2012-02-09 Created: 2012-02-09 Last updated: 2012-02-09Bibliographically approved

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