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- Title
Effect of protein kinase C and insulin on Na<sup>+</sup>/H<sup>+</sup> exchange in red blood cells of essential hypertensives.
- Authors
Ceolotto, G; Sartori, M; Felice, M; Clari, G; Bordin, L; Semplicini, A
- Abstract
The kinetic properties of sodium-proton exchange are abnormal in human red blood cells of hypertensive patients and it has been demonstrated that the transport protein undergoes post-translational modifications able to affect its kinetic properties. Protein kinase C (PKC) activation decreases the affinity constant for intracellu-lar protons while insulin increases the maximal rate of proton translocation. The present study therefore aimed to examine the relationships among PKC activity, fasting insulin levels and the kinetic behaviour of sodium-proton exchange in red blood cells from 20 normoten-sives and 36 hypertensives. In comparison with normotensive subjects, hypertensive patients had higher body mass index (26.2 ± 0.7 vs 23.6 ± 0.6 kg/m[SUP2], P < 0.05), higher fasting insulin levels (93.2 ± 10.8 vs 38.6 ± 2.9 pmol/L), increased maximal velocity of proton translocation (37.9 ± 2.7 vs 27.6 ± 1.9 mmol/L per cell 3 h, P < 0.05), and reduced Hill's coefficient (1.6 ± 0.1 vs 2.0 ± 0.1, P < 0.01) of sodium-proton exchange. Basal PKC activity of the cytosol and membrane was similar in the study groups. However, after treatment with 1 μmol/L phorbol 12-myristate 13-acetate (PMA) for 10 min, membrane PKC activity was stimulated to a larger extent in hypertensives (to 181 ± 8 pmol/min/mg protein) than in normotensives (to 136 ± 6 pmol/min/mg protein, P < 0.01). The PMA stimulated PKC activity was positively correlated to fasting insulin levels (r = 0.59, P < 0.01). Stimulation of membrane PKC by PMA corrected the low Hill's coefficient for H+ activation of sodium-proton exchange in the hypertensives, while the constant for half maximal activation for intracellular protons (ie, the affinity for intracellular protons) decreased to a similar extent in both groups. The maximal transport rate was unaffected by PMA. These results indicate that the abnormal proton activation of red...
- Subjects
PROTEIN kinase C; HYPERTENSION; INSULIN
- Publication
Journal of Human Hypertension, 1999, Vol 13, Issue 5, p321
- ISSN
0950-9240
- Publication type
Article
- DOI
10.1038/sj.jhh.1000804