Skip to main content
SpringerLink
Log in

Implication of BBM lipid composition and fluidity in mitigated alkaline phosphatase activity in renal cell carcinoma

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Previous study has documented reduced alkaline phosphatase (ALP) activity in brush border membrane (BBM) isolated from renal cell carcinoma (RCC). Diminished activity of ALP is associated with alteration in both increased K m as well as decreased V max of enzyme suggests that there may be a change in the conformation of enzyme as well as decreased number of ALP active molecules. The present study was conducted to find out any role of BBM lipid composition and its fluidity in diminished activity of alkaline phosphatase in renal cell carcinoma. Total phospholipids and glycolipids were significantly augmented in BBM from RCC as compared to control. Fractional analysis of total phospholipids revealed significantly increased phosphatidylethanolamine. Decreased fractions of sphingomyelin and phosphatidylinositol were observed. Cholesterol-to-total phospholipid molar ratios in tumor BBM was a significantly lower in tumor BBM. A significant reduction in polarization and microviscosity was found in BBM from RCC. Therefore, we conclude that alteration in membrane lipid composition and fluidity may play a substantial role in reduced activity of ALP in RCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Adiga GU, Dutcher JP, Larkin M, Garl S, Koo J (2009) Characterization of bone metastases in patients with renal cell carcinoma. Br J Urol Int 93:1237–1240

    Article  Google Scholar 

  2. Ericcson S (1965) Electron microscopic observation on specialization of the cell surface in RCC. Lab Invest 14:435–477

    Google Scholar 

  3. McComb RB, Bowers GN, Posen S (1979) Alkaline phosphatase. Plenum, New York

    Book  Google Scholar 

  4. Harries H (1990) The human alkaline phosphatases: what we know what we don’t know. Clin Chim Acta 186:133–150

    Article  Google Scholar 

  5. Low MG, Saltiel AR (1998) Structure and functional roles of glycosyl-phosphatidyl inositol in membranes. Science 139:268–275

    Google Scholar 

  6. Beertsen W, Bos TVD (1992) Alkaline phosphatase induce the mineralization of sheets of collagen implanted subcutaneously in the rats. J Clin Invest 89:1974–1980

    Article  PubMed  CAS  Google Scholar 

  7. Weiss MJ, Cole DEC, Ray K, Whyte MP, Lafferty MA, Mulivor RA, Harris H (1988) A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. Proc Natl Acad Sci 85:7666–7669

    Article  PubMed  CAS  Google Scholar 

  8. McLean FM, Keller PJ, Gange BR, Walters SA, Wutheir RE (1987) Disposition of preformed minerals in matrix vesciles, internal localization and association with alkaline phosphatase. J Biol Chem 262:10481–10488

    PubMed  CAS  Google Scholar 

  9. Anderson HC (1989) Biology of disease, mechanism of mineral formation in bone. Lab Invest 60:320–330

    PubMed  CAS  Google Scholar 

  10. Zucchini CZ, Bianchini M, Valvassori L et al (2004) Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with liver/bone/kidney alkaline phosphatase. Bone 34:672–679

    Article  PubMed  CAS  Google Scholar 

  11. Shigenari A, Ando A, Baba T, Yamamoto T, Katsuoka Y, Inoko H (1998) Characterization of alkaline phosphatase gene expressed in seminoma by cDNA cloning. Cancer Res 58:5079–5082

    PubMed  CAS  Google Scholar 

  12. Prasad R, Lambe S, Kaler P, Pathania S, Kumar S, Attri S, Singh SK (2005) Ectopic expression of alkaline phosphatase in proximal tubular brush border membrane of human renal cell carcinoma. Biochim Biophys Acta 1741:240–245

    Article  PubMed  CAS  Google Scholar 

  13. Benga G, Holmes RP (1984) Interaction between components in biological membranes and their implications for membrane function. Prog Biophys Mol Biol 43:195–257

    Article  PubMed  CAS  Google Scholar 

  14. Meer GV, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112–124

    Article  PubMed  Google Scholar 

  15. Prasad R, Kumar V, Kumar R, Singh KP (1999) Thyroid hormone modulates zinc transport activity of rat intestinal and renal brush border membrane. Am J Physiol 276:E774–E782

    PubMed  CAS  Google Scholar 

  16. Lowry OH, Rosebrough NJ, Farr AL, Randall RL (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  17. Levi M, David MJ, Wieb B, Van Der Meer BW (1989) Role of BBM lipid composition and fluidity in impaired renal Pi transport in aged rat. Am J Physiol 256:F85–F94

    PubMed  CAS  Google Scholar 

  18. Zlatkis A, Zak B, Boyle A (1953) A new method for the direct determination of serum cholesterol. J Lab Clin Med 42:486–492

    Google Scholar 

  19. Shincitzky M, Barenholz Y (1978) Fluidity-parameters of lipid regions determined by fluorescence polarization. Biochim Biophys Acta 515:367–394

    Article  Google Scholar 

  20. Van Blitterswijk WJ, Van Hoeven RP, Vander Meer BW (1981) Lipid structural order parameters (reciprocal of fluidity) in biomembranes derived from steady-state fluorescence depolarization measurements. Biochim Biophys Acta 644:323–332

    Article  PubMed  Google Scholar 

  21. Prasad R, Kumar V (2005) Thyroid hormones stimulate Na+-Pi transport activity in rat renal brush border membranes: role of membrane lipid composition and fluidity. Mol Cell Biochem 268:75–82

    Article  PubMed  CAS  Google Scholar 

  22. Giancotti FG, Mainiero F (1994) Integrin-mediated adhesion and signaling in tumorigenesis. Biochim Biophys Acta 1198:47–64

    PubMed  CAS  Google Scholar 

  23. Brasitus TA, Schaechter D, Mamouneas TG (1979) Functional interactions of lipids and proteins in rat intestinal microvillus membranes. Biochemsitry 18:4136–4144

    Article  CAS  Google Scholar 

  24. Proulx P (1991) Structure-function relationship in intestinal brush border membranes. Biochim Biophys Acta 1071:255–271

    Article  PubMed  CAS  Google Scholar 

  25. Kiebzak GM, Sacktor B (1986) Effect of age renal conservation of phosphate in the rat. Am J Physiol 20:F399–F407

    Google Scholar 

  26. O’Bryan D, Lowenstein LM (1974) Effect of aging on the membrane bound enzyme activities. Biochim Biophys Acta 339:1–9

    Article  PubMed  Google Scholar 

  27. Pratz J, Corman B (1985) Age related changes in enzyme activities, protein content and lipid composition of rat kidney brush border membranes. Biochim Biophys Acta 814:265–273

    Article  PubMed  CAS  Google Scholar 

  28. Noda M, Yoon K, Rodan GA, Koppel DE (1987) High lateral mobility of endogenous and transfected alkaline phosphatase: a phosphatidylinositol-anchored membrane protein. J Cell Biol 105:1671–1677

    Article  PubMed  CAS  Google Scholar 

  29. Hakomori S (1996) Tumor malignancy defined by aberrant glycosylation and sphingo (glyco) lipid metabolism. Cancer Res 56:5309–5318

    PubMed  CAS  Google Scholar 

  30. Van Blitterswijk WJ, Van Der Meer BW, Hilkman H (1987) Quantitative contributions of cholesterol, and the individual classes of phospholipids and their degree of fatty acyl (un)saturation to membrane fluidity measured by fluorescence polarization. Biochemistry 26:1746–1756

    Article  PubMed  Google Scholar 

  31. Friedlander G, Shahedi M, Grimellec C, Amiel C (1988) Increase in membrane fluidity and opening of tight junctions have similar effects on sodium-coupled uptakes in renal epithelial cells. J Biol Chem 263:11183–11188

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We acknowledged Dr. Nandita Kakkar, Department of Histopathology, PGIMER, Chandigarh, for her contribution to the histopathology. This is a part of research project funded by the Department of Biotechnology, New Delhi, India (vide letter no. BT/PR8372/MED/12/345/2006). Council of Scientific and Industrial Research, New Delhi, India, is highly acknowledged for awarding junior and senior research fellowship (vide letter no. 09/141(0166)/2006-EMR-I).

Author information

Authors and Affiliations

  1. Department of Biochemistry, PGIMER, Chandigarh, India

    Ujjawal Sharma, Deeksha Pal, Ragini Khajuria & Rajendra Prasad

  2. Department of Urology, PGIMER, Chandigarh, India

    Shrawan Kumar Singh & Arup Kumar Mandal

Authors
  1. Ujjawal Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shrawan Kumar Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Deeksha Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ragini Khajuria
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arup Kumar Mandal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rajendra Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajendra Prasad.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharma, U., Singh, S.K., Pal, D. et al. Implication of BBM lipid composition and fluidity in mitigated alkaline phosphatase activity in renal cell carcinoma. Mol Cell Biochem 369, 287–293 (2012). https://doi.org/10.1007/s11010-012-1391-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-012-1391-y

Keywords

Search

Navigation