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Involvement of Cellular Membranes and their Lipids in Nucleation of Stone Forming Crystals

Published online by Cambridge University Press:  10 February 2011

S. R. Khan ,
J. M. Fasano ,
R. Backov  and
D. R. Talham
S. R. Khan
Affiliation:
Department of Pathology; University of Florida, Gainesville, FL, khan@ufl.edu
J. M. Fasano
Affiliation:
Department of Pathology; University of Florida, Gainesville, FL, khan@ufl.edu
R. Backov
Affiliation:
Department of Chemistry, University of Florida, Gainesville, FL, khan@ufl.edu
D. R. Talham
Affiliation:
Department of Chemistry, University of Florida, Gainesville, FL, khan@ufl.edu
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Abstract

More than 80% of human kidney stones consist of calcium oxalate and/or calcium phosphate. Human urine is generally metastable with respect to these salts and their nucleation is heterogeneous. Based on: 1. ultrastructural and immunohistochemical studies of stones in which cellular degradation products and lipids were commonly seen in association with calcific crystals and 2. in vivo studies of nephrolithiasis in rat models where calcium oxalate (CaOx) and calcium phosphate (CaP) crystals almost always formed and seen in association with cell membranes, we proposed that membranes and their lipids are involved in crystallization of these salts. To test our hypothesis we isolated organic matrix of kidney stones, its lipid contents and membrane vesicles from epithelial cells of rat kidney and incubated them in metastable solution of CaOx. Both membrane vesicles and matrix from the stones supported crystallization of CaOx and crystals formed in association with the membranes. Lipids of the stone matrix appeared better nucleators than whole matrix. Urine spends only minutes within the kidneys thus any nucleation which can lead to stone formation has to occur rapidly. In studies described here, we demonstrate that under specific circumstances relevant to conditions in the kidney, membrane vesicle- supported CaOx crystallization can occur within seconds, demonstrating the possibility of such events happening in the kidneys. We also studied CaOx monohydrate (COM) precipitation at Langmuir monolayers of dipalmitoylphosphatidylglecerol (DPPG), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS) showed precipitation to be heterogeneous and selective with a majority of crystals orienting with the 101 face of COM facing the monolayer. Our results show that membrane lipids can initiate nucleation of calcium oxalate crystals in solutions similar to those present in the kidneys. In addition these crystals form within the time urine spends inside the renal tubules demonstrating for the first time the likelihood of occurrence of such a phenomenon in the kidneys during stone formation.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 599: Symposium DD – Mineralization in Natural & Synthetic Biomaterials , 1999 , 269
Copyright
Copyright © Materials Research Society 2000

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References

1. Sirekowsky, R., Finlayson, B., Landes, R., Finlayson, C.D. and Sirekowsky, N., Investigative Urology, 15, 438, 1978.Google Scholar
2. Khan, S.R, in Calcification in Biological Systems, edited by Bonnuci, E. (CRC Press, Boca Raton, Florida, 1992) p 345–363.Google Scholar
3. Otnes, B., Scand. J. Urol. Nephrol., Suppl. 71, 1983.Google Scholar
4. Finlayson, B., Urol. Clin. North Am., 1, 181, 1974.Google Scholar
5. Kok, D.J. and Khan, S.R., Kid. Int. 46, 847, 1994.Google Scholar
6. Kok, D.J., Scan. Microsc. 10, 471, 1996.Google Scholar
7. Khan, S. R., Scan. Microsc., 9, 89, 1995.Google Scholar
8. Khan, S.R., Atmani, F., Glenton, P., Hou, Z C, Talham, D.R., Khurshid, M., Calcif. Tissue Intl. 59, 357, 1996.Google Scholar
9. Khan, S.R., Shevock, P.N. Hackett, R.L., Calcif. Intl., 46, 116, 1989.Google Scholar
10. Khan, S.R., Whalen, P.O., Glenton, P.A. J Crystal Growth, 134, 211, 1993.Google Scholar
11. Roberts, G. G., Langmuir-Blodgett Films, Plenum Press, New York, 1990.Google Scholar
12. Mann, S., Heywood, B. R., Rajam, S., Birchall, J. D., Nature, 334, 692, 1988.Google Scholar
13. Whipps, S., Khan, S. R., Opalko, F. J., Backov, R. and Talham, D. R., J. Cryst. Growth, 192, 243, 1998.Google Scholar
14. Backov, R., Khan, S. R., Mingotaud, C., Byer, K., Lee, C. M., Talham, D. R., J. Am. Soc. Nephrol. 10, S359, 1999.Google Scholar
15. Backov, R., Lee, C.M., Khan, S.R., Mingotaud, C., Fanucci, G.E. and  Talham, D.R., Langmuir (submitted).Google Scholar
16. Bigelow, M. W., Wiessmer, J. H., Kleinman, J. G. and  Mandel, N. S., Calcif. Tissue Int. 4, 375, 1997.Google Scholar
17. Sela, J., Schwartz, Z., Swain, L.D. and  Boyan, B.D., in Calcification in Biological Systems, edited by Bonnuci, E., (CRC Press, Boca Raton, Florida, 1992) pp. 73–105.Google Scholar
18. Kim, K. M., Fed. Proc., 25, 156, 1976.Google Scholar
19. Kim, K M., Scanning Electron Microsc., 3, 1151, 1986.Google Scholar
20. Varma, V.A. and  Kim, K.M., Scanning Electron Microsc., 4, 1567, 1985.Google Scholar
21. Schoen, F.J., Harasaki, H., Kim, K.M., Anderson, H.C. and  Levy, R.J., J. Biomed. Mat. Res., 22, 11, 1988.Google Scholar
22. Khan, S.R. and  Wilkinson, E.J., Human Pathol., 16, 732, 1985.Google Scholar
23. Boyan, B.D., Swain, L.D. and  Everett, M.M., in Calcification in Biological Systems, edited by Bonnuci, E., (CRC Press, Boca Raton, Florida, 1992), pp. 129–156.Google Scholar
24. Boskey, A.L., Clin. Orthop. Rel. Res., 157, 225, 1981.Google Scholar
25. Boskey, A.L., Clin. Orthop. Rel. Res. 281, 244, 1992.Google Scholar
26. Khan, S., RI and Hackett, R.L., Scanning Electron Microsc. 2, 761, 1986.Google Scholar
27. Watanabe, T., Tohoku J. Exp. Med., 107, 345, 1972.Google Scholar
28. Khan, S.R., Shevock, P.N. and  Hackett, R.L., Calcif. Tissue Intl., 42, 91, 1988.Google Scholar
29. Khan, S.R., Maslamani, S.A., Atmani, F., Glenton, P.A., Opalko, F.J., Thamilselvan, S., and Hammett-stabler, C., Calcif. Tissue Intl., In Press.Google Scholar
30. Thamilselvan, S., Hackett, R.L. and  Khan, S.R., J. Am. Soc. Nephrol. 10: S452, 1999 Google Scholar