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Carraro-Lacroix LR, Girardi AC, Malnic G: Long-term regulation of vacuolar H (+)-ATPase by angiotensin II in proximal tubule cells. Pflugers Arch. 2009 Sep;458(5):969-79. Epub 2009 Apr 26. Long-term effects of angiotensin II (Ang II) on vacuolar H (+)-ATPase were studied in a SV40-transformed cell line derived from rat proximal tubules (IRPTC). Using pH (i) measurements with the fluorescent dye BCECF, the hormone increased Na (+)-independent pH recovery rate from an NH (4) Cl pulse from 0.066 +/- 0.014 pH U/min (n = 7) to 0.14 +/- 0.021 pH U/min (n = 13; p < 0.05) in 10 h Ang II (10 (-9) M)-treated cells. The increased activity of H (+)-ATPase did not involve changes in mRNA or protein abundance of the B2 subunit but increased cell surface expression of the V-ATPase. Inhibition of tyrosine kinase by genistein blocked Ang II-dependent stimulation of H (+)-ATPase. Inhibition of phosphatidylinositol-3-kinase (PI3K) by wortmannin and of p38 mitogen-activated protein kinase (MAPK) by SB 203580 also blocked this effect. Thus, long-term exposure of IRPTC cells to Ang II causes upregulation of H (+)-ATPase activity due, at least in part, to increased B2 cell surface expression. This regulatory pathway is dependent on mechanisms involving tyrosine kinase, p38 MAPK, and PI3K activation. |
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