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The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2

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Summary

Mechanical forces applied to cultured bone cells induce the production of cAMP via stimulation of the formation of prostaglandin E2 (PGE2) and its release into the medium, resulting in stimulation of adenylate cyclase. In this paper we show that either the antibiotic gentamycin (100 μg/ml) or antiphospholipid antibodies (0.1%) which bind to membrane phospholipids abolish cAMP formation induced by mechanical forces; exogenously added arachidonic acid or PGE2 stimulates cAMP formation, even in the presence of these agents. Addition of exogenous phospholipase A2 (but not phospholipase C) causes an increase in the formation of cAMP in bone cells, a response that is also inhibited by gentamycin or antiphospholipase antibodies. These observations suggest that mechanical forces exert their effect on bone cells via the following chain of events: (1) activation of phospholipase A2, (2) release of arachidonic acid, (3) increased PGE synthesis, (4) augmented cAMP production.

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References

  1. Glücksmann A (1942) The role of mechanical stress in bone formation in vitro. J Anat 76:231–239

    PubMed  Google Scholar 

  2. Sömjen D, Binderman I, Berger E, Harell A (1980) Bone remodelling induced by physical stress is prostaglandin mediated. Biochim Biophys Acta 627:91–100

    PubMed  Google Scholar 

  3. Russel DH (1980) Ornithine decarboxylase as a biological pharmacological tool. Pharmacology 20:117–120.

    Google Scholar 

  4. Kenyon GL, Reed GH (1983) Creatine kinase: structure activity relationships. Adv Enzymol 54:367–426

    PubMed  CAS  Google Scholar 

  5. Bessman SP, Carpenter CL (1985) The creatine-creatine phosphate energy shuttle. Ann Rev Biochem 54:831–862

    Article  PubMed  CAS  Google Scholar 

  6. Watts DS (1973) Creatine kinase (adenosine 5′-triphosphate creatine phosphotransferase). In: Boyer P (ed) The enzymes Vol 8. 2. Academic Press, New York, pp 383

    Google Scholar 

  7. Sömjen D, Yariv M, Kaye AM, Korenstein R, Fischler H, Binderman I (1982) Ornithine decarboxylase activity in cultured bone cells is activated by bone-seeking hormones and physical stimulation. Adv Polyamine Res 4:713–718

    Google Scholar 

  8. Sömjen D, Kaye AM, Binderman I (1985) Stimulation of creatine kinase BB activity by parathyroid hormone and by prostaglandin E2 in cultured bone cells. Biochem J 225:591–596

    PubMed  Google Scholar 

  9. Kaye AM, Reiss N, Weisman Y, Binderman I, Sömjen D (1986) Hormonal regulation of creatine kinase BB. In: Brautbaur N (ed) Myocardial and skeletal muscle bioenergetics. Plenum Press, New York, pp 83–101

    Google Scholar 

  10. Folkert VW, SchlendorffD (1983) Relationship between prostaglandin synthesis and phospholipid turnover in rat glomeruli. Adv Prostaglandin Thromboxane Leukotriene Res 11:513–516

    CAS  Google Scholar 

  11. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  12. Andre-Schwartz J, Datta SK, Shoenfeld Y, Isenberg DA, Stollar BD, Schwartz RS (1984) Binding of cytoskeletal proteins by monoclonal anti-DNA lupus anti-antibodies. Clin Immunol Immunopathol 31:261–271

    Article  PubMed  CAS  Google Scholar 

  13. Jacob L, Tron F, Bach J-F, Louvard D (1984) The anti-DNA antibody also binds to cell surface proteins. Proc Natl Acad Sci USA 81:3843–3845

    Article  PubMed  CAS  Google Scholar 

  14. Sömjen D, Sömjen Z, Sömjen U, Kaye AM, Harell A, Binderman I (1987) Parathyroid hormone induction of creatine kinase activity and DNA synthesis is mimicked by phospholipase C, diacylglycerol and phorbol ester. Biochim Biophys Acta 931:215–223

    Article  PubMed  Google Scholar 

  15. Schwertz DW, Troyer DA, Kreisberg JI, Vankatachalam MA (1985) Pathology and pathogenesis of nephrotoxic membrane damage. Transplant Proc XVII (suppl), 1:63–71

    Google Scholar 

  16. Fujimoto Y, Akamatsu N, Hattori A, Fujita T (1984) Stimulation of prostaglandin E2 synthesis by exogenous phospholipase A2 and C in rabbit kidney medulla slices. Biochem J 218:69–74

    PubMed  CAS  Google Scholar 

  17. Schacht J (1978) Purification of phosphoinositides by chromatography on immobilized neomycin. J Lipid Res 19:1063–1067

    PubMed  CAS  Google Scholar 

  18. Carlier MB, Laurent G, Claes PJ, Vanderhaeghe HJ, Tulkens PM (1983) Inhibition of lysosomal phospholipases by aminoglycoside antibiotics in vitro: comparative studies. Antimicrob Agents Chemother 23:440–449

    PubMed  CAS  Google Scholar 

  19. Lipsky JJ, Lietman PS (1982) Aminoglycoside inhibition of renal phosphatidyl inositol phospholipase. CJ Pharmacol Exp Ther 220:287–292

    CAS  Google Scholar 

  20. Hostestler KY, Hall LB (1982) Inhibition of kidney lysosomal phospholipases A and C by aminoglycoside antibiotics: possible mechanism of aminoglycoside toxicity. Proc Natl Acad Sci USA 79:1663–1667

    Article  Google Scholar 

  21. Burch RM, Luini A, Axelrod J (1986) Proc Natl Acad Sci USA 83:7201–7205

    Article  PubMed  CAS  Google Scholar 

  22. Siess W, Lapetina EG (1986) Neomycin inhibits inositol phosphate formation in human platelets stimulated by thrombin but not other agonists. FEBS Lett 207:53–57

    Article  PubMed  CAS  Google Scholar 

  23. Langeland N, Haarr L, Holmsen H (1986) Evidence that neomycin inhibits HSV 1 infection of BHK cells. Biochem Biophys Res Commun 141:198–203

    Article  PubMed  CAS  Google Scholar 

  24. Ramsammy L, Kaloyanides GJ (1986) Gentamycin perturbs the phosphotyckl inositol cascade as assessed by inhibition of protein kinase C activation in rat renal cortex. Kidney Int 29:308

    Google Scholar 

  25. Krieger H, Leddy JP, Breckenridge RT (1975) Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor 1Ya). Blood 46:189–197

    PubMed  CAS  Google Scholar 

  26. Schlondorff D, Perez J, Satriano JA (1985) Differential stimulation of PGE2 synthesis in mesangial cells by angiotensin and A23/87. Am J Physiol 248:C119-C126

    PubMed  CAS  Google Scholar 

  27. Zor U, Ben-Dori R, Maoz I, Wallach D, Gurari-Rotman D (1982) Inhibition by glucocorticosteriod hormones of interferon and prostaglandin E induction by poly(rI).poly(rC). J Gen Virol 63:359–363

    Article  PubMed  CAS  Google Scholar 

  28. Nishizuka Y (1986) Studies and perspectives of protein kinase C. Science 233:305–312

    Article  PubMed  CAS  Google Scholar 

  29. Rozengurt E (1986) Early signals in the mitogenic response. Science 234:161–166

    Article  PubMed  CAS  Google Scholar 

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Binderman, I., Zor, U., Kaye, A.M. et al. The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2 . Calcif Tissue Int 42, 261–266 (1988). https://doi.org/10.1007/BF02553753

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  • DOI: https://doi.org/10.1007/BF02553753

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