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Molecular species of membrane phospholipids containing arachidonic acid and linoleic acid contribute to the interindividual variability of red blood cell Na+-Li+ countertransport: In vivo and in vitro evidence

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Summary

Previous studies indicate a particular sensitivity of red blood cell Na+-Li+ countertransport activity to small variations in the fatty acid composition of membrane phospholipids. To assess whether the interindividual variability of Na+-Li+ countertransport is related to differences in the species pattern of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in vivo, the molecular species composition of PC and PE as well as the kinetics of Na+-Li+ countertransport were analyzed in parallel in normo- and hyperlipidemic donors. Both in diacyl PC and in diacyl-PE the species 16∶0/20∶4 and 16∶0/18∶2 were, respectively, positively and negatively related to the apparent maximal velocity of Na+-Li+ countertransport. The sum of all species with 20∶4 at sn2 of diacyl-PE exhibited a strong positive (r = 0.82, 2p < 0.001), and those containing 18∶2 a negative correlation (r = −0.63, 2p < 0.01) to the transport activity. Essentially similar connections were observed between these species and the apparent affinity of the transport system for intracellular Na+. To evaluate whether the associations between molecular species of membrane phospholipids and Na+-Li+ countertransport activity were indicative of a causal relationship, the species 16∶0/20∶4-PC and 16∶0/18∶2-PC were selectively introduced into the erythrocyte membrane by means of the PC-specific transfer protein. Replacement of 11% of native PC by 16∶0/18∶2-PC inhibited the transport rate by about 25%. Exchange of 6 and 9% of PC with 16∶0/20∶4-PC, in contrast, accelerated the transport rate by 30 and 60%, respectively. The accordance between the in vivo relations and the results of the in vitro modification strongly suggests that elevations and reductions in the arachidonic acid and linoleic acid content of membrane PC and PE contribute to the interindividual variability of red blood cell Na+-Li+ counter-transport activity and its acceleration in hyperlipidemias.

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References

  1. Arvidson, G.A.E. 1968. Structural and metabolic heterogeneity of rat liver glycerophosphatides. Eur. J. Biochem. 4:478–486

    Google Scholar 

  2. Brenner, R.R. 1990. Endocrine control of fatty acid desaturation. Biochem. Soc. Trans. 18:773–775

    Google Scholar 

  3. Canessa, M., Adragna, N., Solomon, H.S., Connolly, T.M., Tosteson, D.C. 1980. Increased sodium-lithium countertransport in red cells of patients with essential hypertension. N. Engl. J. Med. 302:772–776

    Google Scholar 

  4. Carr, S.J. Thomas, T.H., Laker, M.F., Wilkinson, R. 1990. Elevated sodium-lithium countertransport: a familial marker of hyperlipidaemia and hypertension? J. Hypertension 8:139–146

    Google Scholar 

  5. Corrocher, R., Steinmayr, M., Ruzzenente, O., Brugnara, C., Bertinato, L., Mazzi, M., Furri, C., Bonfanti, F., de Sandre, G. 1985. Elevation of red cell sodium-lithium countertransport in hyperlipidemias. Life Sci. 36:649–655

    Google Scholar 

  6. Doria, A., Fioretto, P., Avogaro, A., Carraro, A., Morocutti, A., Trevisan, R., Frigato, F., Crepaldi, G., Viberti, G.C. 1991. Insulin resistance is associated with high sodium lithium countertransport in essential hypertension. Am. J. Physiol. 261:E684-E691

    Google Scholar 

  7. Duhm, J., Becker, B.F. 1977. Studies on the lithium transport across the red cell membrane. IV. Interindividual variations in the Na+-dependent Li+ countertransport system of human erythrocytes. Pfluegers Arch. 370:211–219

    Google Scholar 

  8. Engelmann, B., Op den Kamp, J.A.F., Roelofsen, B. 1990. Replacement of molecular species of phosphatidylcholine: influence on erythrocyte Na transport. Am. J. Physiol. 258:C682-C691

    Google Scholar 

  9. Engelmann, B., Duhm, J. 1991. Effect of cholesterol and dipalmitoyl phosphatidylcholine enrichment on the kinetics of Na+-Li+ exchange of human erythrocytes. J. Membrane Biol. 122:231–238

    Google Scholar 

  10. Engelmann, B., Duhm, J., Schönthier, U.M., Streich, S. 1993. Relations of sodium-lithium countertransport kinetics to plasma and red cell membrane phospholipids in hyperlipidemia. Atherosclerosis (in press)

  11. Engelmann, B., Schönthier, U.M., Richter, W.O., Duhm, J. 1992. Changes of membrane phospholipid composition of human erythrocytes in hyperlipidemias. II. Increases in distinct molecular species of phosphatidylethanolamine and phosphatidylcholine containing arachidonic acid. Biochim. Biophys. Acta 1165:38–44

    Google Scholar 

  12. Hasstedt, S.J., Wu, L.L., Ash, K.O., Kuida, H., Williams, R.R. 1988. Hypertension and sodium-lithium countertransport in Utah pedigrees: Evidence for major locus inheritance. Am. J. Hum. Genet. 43:14–22

    Google Scholar 

  13. Hullin, F., Bossant, M.-J., Salem, N., Jr. 1991. Aminophospholipid molecular species asymmetry in human erythrocyte plasma membrane. Biochim. Biophys. Acta 1061:15–25

    Google Scholar 

  14. Levy, R., Livne, A. 1984. The erythrocyte membrane in essential hypertension. Characterization of the temperature dependence of lithium efflux. Biochim. Biophys. Acta 769:41–48

    Google Scholar 

  15. Mangili, R., Bending, J.J., Scott, G., Li, L.K., Gupta, A., Viberti, G.C. 1988. Increased sodium-lithium countertransport in red cells of patients with insulin-dependent diabetes and nephropathy. N. Engl. J. Med. 318:146–150

    Google Scholar 

  16. Morrison, W.R., Smith, I.M. 1964. Preparation of fatty acid methylesters and dimethylacetals from lipids with boron-trifluoride methanol. J. Lip. Res. 5:600–608

    Google Scholar 

  17. Myher, J.J., Kuksis, A., Pind, S. 1989. Molecular species of glycerophospholipids and sphingomyelins of human erythrocytes: Improved method of analysis. Lipids 24:396–407

    Google Scholar 

  18. Naftilan, A.J., Dzau, V.J., Loscalzo, J. 1986. Preliminary observations on abnormalities of membrane structure and function in essential hypertension. Hypertension 8(suppl.II):174–179

    Google Scholar 

  19. Nosadini, R., Semplicini, A., Fioretto, P., Lusiani, L., Trevisan, R., Donadon, V., Zanette, G., Nicolosi, G.L., Dall'Aglio, V., Zanuttini, D., Viberti, G.C. 1990. Sodiumlithium countertransport and cardio-renal abnormalities in essential hypertension. Hypertension 18:191–198

    Google Scholar 

  20. Ollerenshaw, J.D., Heagerty, A.M., Bing, R.F., Swales, J.D. 1987. Abnormalities of erythrocyte membrane fatty acid composition in human essential hypertension. J. Hum. Hypertension 1:9–12

    Google Scholar 

  21. Reaven, G.M. 1988. The Banting lecture 1988: role of insulin resistance in human disease. Diabetes 37:1595–1607

    CAS  PubMed  Google Scholar 

  22. Rose, H.G., Oklander, M.J. 1965. Improved procedure for the extraction of lipids from human erythrocytes. J. Lip. Res. 65:428–431

    Google Scholar 

  23. Sarkadi, B., Alifimoff, J.K., Gunn, R.B., Tosteson, D.C. 1978. Kinetics and stoichiometry of Na-dependent Li transport in human red blood cells. J. Gen. Physiol. 72:249–265

    Google Scholar 

  24. Stubbs, C.D., Smith, A.D. 1984. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim. Biophys. Acta 779:89–137

    Google Scholar 

  25. Takamura, H., Narita, H., Park, H.J., Tanaka, K., Matsuura, T., Kito, M. 1987. Differential hydrolysis of phospholipid molecular species during activation of human platelets with thrombin and collagen. J. Biol. Chem. 262:2262–2269

    Google Scholar 

  26. Turner, S.T., Weidman, W.H., Michels, V.V., Reed, T.J., Ormson, C.L., Fuller, T., Sing, C.F. 1990. Distribution of sodium-lithium countertransport and blood pressure in Caucasians five to eighty-nine years of age. Hypertension 13:378–391

    Google Scholar 

  27. Van Meer, G., Op den Kamp, J.A.F. 1982. Transbilayer movement of various phosphatidylcholine species in intact human erythrocytes. J. Cell. Biochem. 19:193–204

    Google Scholar 

  28. Wieth, J.O. 1970. Paradoxical temperature dependence of sodium and potassium fluxes in human red cells. J. Physiol. 207:563–580

    Google Scholar 

  29. Yap, L., Arrazola, A., Soria, F., Diez, J. 1989. Is there increased cardiovascular risk in essential hypertensive patients with abnormal kinetics of red blood cell sodium-lithium countertransport? J. Hypertension 7:667–673

    Google Scholar 

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The authors wish to thank Dr. W.O. Richter (II. Medizinische Klinik, Klinikum Großhadern, Universität München) for selection of the patients and Dr. T. Brosche (Universität ErlangenNürnberg) for gaschromatographic analyses. This study was supported in part by a grant of the Wilhelm-Sander-Stiftung to B.E.

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Engelmann, B., Duhm, J., Schönthier, U.M. et al. Molecular species of membrane phospholipids containing arachidonic acid and linoleic acid contribute to the interindividual variability of red blood cell Na+-Li+ countertransport: In vivo and in vitro evidence. J. Membarin Biol. 133, 99–106 (1993). https://doi.org/10.1007/BF00233791

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  • DOI: https://doi.org/10.1007/BF00233791

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