Lens epithelial cell response to isoforms of platelet-derived growth factor

  • Marcus Knorr
  • Kerstin Wunderlich
  • Klaus-P. Steuhl
  • Jürgen Hoppe
Laboratory Investigations
Received:
Accepted:

Abstract

It has been reported previously that platelet derived growth factor (PDGF) may play an important role in the regulation of lens growth and differentiation. To evaluate PDGF-induced effects at the cellular level, we investigated the response of cultured bovine lens epithelial cells (BLEC) to PDGF-AB, -AA, and -BB isoforms at the cellular level. Stimulation of BLEC with PDGF isoforms showed no increase in cell proliferation under the culture conditions of this study. In contrast, measurement of cytosolic free calcium concentration ([Ca2+]i), which has been shown to be an important second messenger for controlling multiple cellular processes in the lens, revealed a dose-dependent rise in [Ca2+]i upon stimulation with PDGF-AB and -BB isoforms. PDGF-AA used in similar concentrations was not effective. Our data suggest that PDGF-AB and -BB may play a role in the regulation of cellular functions in BLEC via modulation of intracellular calcium homeostasis.

Keywords

Cell Response Calcium Concentration Cellular Function Intracellular Calcium Cellular Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Baird A, Esch F, Mormese P (1986) Molecular characterization of fibroblast growth factor: distribution and biological activities in various tissues. Recent Prog Horm Res 42:143–205PubMedGoogle Scholar
  2. 2.
    Balk SD, Polimeni PI, Hoon BS, LeStergeon DN, Mitchell RS (1979) Proliferation of Rous sarcoma virus-infected, but not normal chicken fibroblasts in a medium of reduced calcium and magnesium concentration. Proc Natl Acad Sci USA 76:3913–3916PubMedGoogle Scholar
  3. 3.
    Beebe DC, Silver MH, Belcher KS, Wyk JJ van, Svoboda ME, Zelenka PS (1987) Lentropin, a protein that controls lens fiber formation is related functionally and immunologically to the insulin-like growth factors. Proc Natl Acad Sci USA 84:2327–2330PubMedGoogle Scholar
  4. 4.
    Berridge MJ, Taylor CW (1988) Inositol trisphosphate and calcium signaling. Cold Spring Harbor Symposia on Quantitive Biology, vol LIII. Cold Spring Harbor Press, New York, pp 927–933Google Scholar
  5. 5.
    Block LH, Edmonds LR, Vogt E, Sacchanidis A, Vetter W, Hoppe J (1989) Ca2+-channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle cells. Proc Natl Acad Sci USA 86:2388–2394PubMedGoogle Scholar
  6. 6.
    Brewitt B, Clark JI (1988) Growth and transparency in the lens, an epithelial tissue, stimulated by pulses of PDGF. Science 242:777–779PubMedGoogle Scholar
  7. 7.
    Brewitt B, Clark JI (1990) A new method for study of lens development in vitro using pulsative delivery of PDGF or EGF in HL-1 serum-free medium. In Vitro Cell Biol 26:305–413Google Scholar
  8. 8.
    Burgoyne RD, Morgan A, O'Sullivan AJ (1989) The control of cytoskeletal actin and endocytosis in intact and permeabilized adrenal chromaffin cells: role of calcium and protein kinase C. Cell Signal 1:323–334PubMedGoogle Scholar
  9. 9.
    Clark JI, Mengel L, Bagg A, Benedek GB (1980) Cortical opacity, calcium concentration and fiber membrane structure in the calf lens. Exp Eye Res 31:399–410PubMedGoogle Scholar
  10. 10.
    Durham ACH, Walton JM (1982) Calcium ions and the control of proliferation in normal and cancer cells. Biosci Resp 2:15–30Google Scholar
  11. 11.
    Gilles RS (1982) Calcium, calmodulin and CAMP and control of cellular proliferation. Trends Biochem Sci 7:233–235Google Scholar
  12. 12.
    Glasser D, Rattke N, Iwig M (1979) Bovine lens epithelium: a suitable model for studying growth control mechanisms. Exp Cell Res 122:281–292PubMedGoogle Scholar
  13. 13.
    Gospodarowicz D, Mescher AL, Brown KD, Birdwell CR (1977) The role of fibroblast growth factor and epidermal growth factor in the proliferative response of the corneal and lens epithelium. Exp Eye Res 25:631–649PubMedGoogle Scholar
  14. 14.
    Hammacher A, Hellman U, Johnsson A, Osterman A, Gunnarsson K, Westermark B, Wasteson A, Heldin CH (1988) A major part of platelet-derived growth factor from human platelets is a heterodimer of one A and one B chain. J Biol Chem 263:16493–16498PubMedGoogle Scholar
  15. 15.
    Hasegawa-Sasaki H (1985) Early changes in inositol lipids and their metabolites induced by platelet-derived growth factor in quiescent Swiss mouse 3T3 cells. Biochem J 232:99–109PubMedGoogle Scholar
  16. 16.
    Heldin CH, Westermark B (1989) Platelet-derived growth factor: three isoforms and two receptor types. Trends Genet 5:108–111PubMedGoogle Scholar
  17. 17.
    Hightower KR (1983) The influence of calcium on protein synthesis in the rabbit lens. Invest Ophthalmol Vis Sci 24:1422–1426PubMedGoogle Scholar
  18. 18.
    Hokin LE (1985) Receptors and phosphoinositide-generated second messengers. Annu Rev Biochem 54:205–235PubMedGoogle Scholar
  19. 19.
    Hoppe J, Weich HA, Eichner W (1989) Preparation of biologically active platelet-derived growth factor type BB from a fusion protein expressed in E. coli. Biochemistry 28:2956–2960PubMedGoogle Scholar
  20. 20.
    Hoppe J, Weich HA, Eichner W, Tatje D (1990) Preparation of biologically active platelet-derived growth factor isoforms AA and AB. Eur J Biochem 187:207–214PubMedGoogle Scholar
  21. 21.
    Irvine RF, Moor RM (1986) Micro-injection of inositol (1,3,4,5)tetrakisphosphate activates sea urchin eggs by a mechanism dependent on extracellular Ca2+. Biochem J 240:917–922PubMedGoogle Scholar
  22. 22.
    Kim HK, Kim JW, Zilberstein A, Margolis B, Kim JG, Schlessinger J, Rhee SG (1991) PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gammal phosphorylation on tyrosine residues 783 and 1254. Cell 65:435–440PubMedGoogle Scholar
  23. 23.
    Knorr M, Locher R, Edmonds D, Vetter W (1986) Effect of atrial natriuretic polypeptide on angiotensin II-induced increase of cytosolic free calcium in cultured smooth muscle cells. J Hypertension 4: S67-S69Google Scholar
  24. 24.
    Knorr M, Locher R, Vogt E, Vetter W, Block LH, Ferracin F, Lefkovits H, Pletscher A (1988) Rapid activation of human platelets by low concentrations of low-density lipoprotein via phosphatidylinositol cycle. Eur J Biochem 172:753–759PubMedGoogle Scholar
  25. 25.
    Knorr M, Wunderlich K, Tatje D, Steuhl KP, Hoppe J, Thiel HJ (1992) Cultured lens epithelial cells express functional platelet-derived growth factor (PDGF) beta-type receptors. Invest Ophthalmol Vis Sci [Suppl ARVO] 33:1037Google Scholar
  26. 26.
    Martinet Y, Bitterman PB, Mornex J-F, Grotendorst GR, Martin GR, Crystal RG (1986) Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity. Nature 319:158–160PubMedGoogle Scholar
  27. 27.
    McAvoy JW, Chamberlain CG (1990) Growth factors in the eye. Prog Growth Factor Res 2:29–43PubMedGoogle Scholar
  28. 28.
    Moenner M, Magnaldo I, L'Allemain G, Barritault D, Pouyssé-gur J (1987) Early and late events induced by FGF on bovine epithelial lens cells are not triggered by hydrolysis of polyphosphoinositides. Biochem Biophys Res Comm 146:32–40PubMedGoogle Scholar
  29. 29.
    Moolenaar WH, Tertoolen LGJ, de Laat SW (1984) Growth factors immediately raise cytosolic free calcium in human fibroblasts. J Biol Chem 259:8066–8069PubMedGoogle Scholar
  30. 30.
    Nister M, Hammacher A, MellströmK, Siegbahn A, Rönnstrand L, Westermark B, Heldin CH (1988) A gliomaderived PDGF A chain homodimer has different functional activities from a PDGF AB heterodimer purified from human platelets. Cell 52:791–797PubMedGoogle Scholar
  31. 31.
    Raines EW, Bowen-Pope DF, Ross R (1990) Platelet-derived growth factor. In: Sporn MB, Roberts AB (eds) Peptide growth factors and their receptors. (Handbook of experimental pharmacology). Springer, Berlin Heidelberg New York, pp 173–262Google Scholar
  32. 32.
    Rasmussen H, Barrett PQ (1984) Calcium messenger system: an integrated view. Physiol Rev 64:938–984PubMedGoogle Scholar
  33. 33.
    Ross R, Raines EW, Bowen-Pope DF (1986) The biology of platelet-derived growth factor. Cell 46:155–169PubMedGoogle Scholar
  34. 34.
    Rozengurt E, Erusalimsky J, Mehmet H, Morris C, Nanberg E, Sinnett-Smith J (1988) Signal transduction in mitogenesis. Further evidence for multiple pathways. Cold Spring Harbor Symposia on Quantitative Biology, vol LIII. Cold Spring Harbor Press, New York, pp 945–954Google Scholar
  35. 35.
    Sachinidis A, Locher R, Vetter W, Tatje D, Hoppe J (1990) Different effects of platelet-derived growth factor isoforms on rat vascular smooth muscle cells. J Biol Chem 265:10238–10243PubMedGoogle Scholar
  36. 36.
    Weinsieder A, Reddan J, Wilson D (1976) Aqueous humor in lens repair and cell proliferation. Exp Eye Res 23:355–363PubMedGoogle Scholar
  37. 37.
    Whitfeld JF, Boynton AL, MacNamus JP, Sikaraska M, Tsang BK (1979) The regulation of cell proliferation by calcium and cyclic AMP. Mol Cell Biochem 27:155–179PubMedGoogle Scholar
  38. 38.
    Williams LT (1989) Signal transduction by platelet-derived growth factor receptor. Science 243:1564–1570PubMedGoogle Scholar
  39. 39.
    Williamson JR, Monck JR (1989) Hormone effects on cellular Ca2+ fluxes. Annu Rev Physiol 51:107–124PubMedGoogle Scholar
  40. 40.
    Zelenka PS, Vu ND (1984) Correlation between phosphatidylinositol degradation and cell division in embryonic chicken lens epithelia. Dev Biol 105:325–329[PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Marcus Knorr
    • 1
  • Kerstin Wunderlich
    • 1
  • Klaus-P. Steuhl
    • 1
  • Jürgen Hoppe
    • 2
  1. 1.University Eye Clinic, Department of General OphthalmologyUniversity of TübingenTübingenGermany
  2. 2.Institute of Physiological ChemistryUniversity of WürzburgWürzburgGermany

Personalised recommendations