Altered Na+/H+ exchanger isoform 1 activity in immortalized lymphoblasts from women with pre-eclampsia: evidence for an intermediate phenotype.

Abstract

Previous studies have demonstrated a raised Na(+) content in leucocytes isolated from women with pre-eclampsia. Increased Na(+)/H(+) exchanger activity is one membrane transport abnormality that may contribute to this phenomenon and may be implicated in the abnormal volume homoeostasis and hypertension associated with the disease. Increased Na(+)/H(+) exchanger activity has been documented in nucleated white blood cells from both pre-eclamptic and post-partum pre-eclamptic women, and may suggest the importance of genetic influences on exchanger activity. In the present study, we used lymphoblasts from women with pre-eclampsia and from age- and gestation-matched normotensive pregnant controls to determine Na(+)/H(+) exchanger activity and intracellular resting pH using fluorimetry and the pH-sensitive dye BCECF-AM [bis(carboxyethyl)carboxyfluorescein acetoxymethyl ester]. Determination of Na(+)/H(+) exchanger protein abundance was performed by Western blotting. Intracellular pH was not significantly different in cells from pre-eclamptic women compared with those from normotensive controls. Na(+)/H(+) exchanger activity was measured when the intracellular pH was clamped at 6.0, and was found to be significantly higher in cells from pre-eclamptic women (20.77+/-0.92 mmol x min(-1) x l(-1)) compared with those from normotensive controls (15.22+/-0.92 mmol x min(-1) x l(-1); P =0.001). Na(+)/H(+) exchanger protein abundance was established to be similar in the two subject groups, suggesting that the turnover number for the Na(+)/H(+) exchanger is increased in the women with pre-eclampsia. These changes in Na(+)/H(+) exchanger activity indicate the importance of genetic factors in determining this particular phenotype, since in this cell culture model of pre-eclampsia it is likely that environmental or hormonal influences present in vivo would have declined. Overactivity of the Na(+)/H(+) exchanger may contribute to the raised intracellular Na(+) concentration reported previously in white blood cells from women with pre-eclampsia.

• Authors: V M Lee, P A Quinn, S C Jennings, A W F Halligan, L L Ng
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 103 Issue 5 Pg. 503-9 (Nov 2002) ISSN: 0143-5221 [Print] England
• PMID: 12401124 (Publication Type: Journal Article)

Chemical References

• Sodium-Hydrogen Exchangers

Topics

• Adult
• Blotting, Western
• Cell Culture Techniques
• Cell Transformation, Viral
• Female
• Genetic Predisposition to Disease
• Humans
• Hydrogen-Ion Concentration
• Lymphocytes (metabolism)
• Phenotype
• Pre-Eclampsia (blood, genetics)
• Pregnancy
• Sodium-Hydrogen Exchangers (blood)