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Effect of an aldose reductase inhibitor on type IV collagen production by human endothelial cells cultured in high glucose

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Summary

Diabetic microangiopathy is characterized by a thickening of capillary basement membranes associated with type IV collagen accumulation. An increase in type IV collagen content of the aortic wall is also observed in macroangiopathy. In order to analyse the importance of the polyol pathway in the development of the collagen metabolism alterations seen in diabetic angiopathy and their prevention by aldose reductase inhibitors, we have studied the effects of sorbinil on the high glucose-induced stimulation of type IV collagen biosynthesis in human umbilical vein endothelial cells. Primary cultures were exposed to high glucose (16.7 mmol/l), with and without 0.11 mmol/l sorbinil, for 3 or 6 days after beginning of confluence. We measured the soluble type IV collagen secreted into the culture medium and the insoluble type IV collagen accumulated in the extracellular matrix and cells, by ELISA. We also studied [14C]proline incorporation into the newly synthesized collagenous and total proteins in the culture supernatant and in the extracellular matrix and cell fraction. High glucose decreased the number of cells and increased the amount of type IV collagen in the culture supernatant and in the extracellular matrix and cell fraction. It also increased proline incorporation into the newly synthesized collagenous and total proteins in the culture supernatant and in the extracellular matrix and cell fraction. Sorbinil corrected all these high glucose-induced alterations. The corrective effects of sorbinil on the proliferation and on type IV collagen metabolism of endothelial cells cultured in high glucose may be attributed to prevention of polyol pathway dysregulation.

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Abbreviations

AGE:

Advanced glycation end product

AR:

aldose reductase

ARI:

aldose reductase inhibitor

BM:

basement membrane

EC:

endothelial cells

GGHG:

glucosyl-galactosyl-hydroxylysyl-collagen glucohydrolase

HUVEC:

human umbilical vein EC

HS:

human serum

PBS:

phosphate-buffered saline

PKC:

protein kinase C

References

  1. Shimomura H, Spiro R (1987) Studies on macromolecular components of human glomerular basement membrane and alterations in diabetes. Decreased levels of heparan sulphate proteoglycan and laminin. Diabetes 36: 374–381

    Article  CAS  PubMed  Google Scholar 

  2. Rasmussen LM, Ledet T (1993) Aortic collagen alterations in human diabetes mellitus. Changes in basement membrane collagen content and in the susceptibility of total collagen to cyanogen bromide solubilisation. Diabetologia 36: 445–453

    Article  CAS  PubMed  Google Scholar 

  3. Lorenzi M, Nordberg J, Toledo S (1987) High glucose prolongs cell-cycle traversal of cultured human endothelial cells. Diabetes 36: 1261–1267

    Article  CAS  PubMed  Google Scholar 

  4. Stout RW (1982) Glucose inibits replication of cultured human endothelial cells. Diabetologia 23: 436–439

    Article  CAS  PubMed  Google Scholar 

  5. Danne T, Spiro M, Spiro R (1993) Effect of high glucose on type IV collagen production by cultured glomerular epithelial, endothelial, and mesangial cells. Diabetes 42: 170–177

    Article  CAS  Google Scholar 

  6. Moritani S, Negishi K, Watanabe T et al. (1991) Glucose-induced production of type IV collagen and laminin P1 from cultured human umbilical vein endothelial cells. J Diabetic Complications 5: 201–203

    Article  CAS  Google Scholar 

  7. Cagliero E, Maiello M, Boeri D, Roy S, Lorenzi M (1988) Increased expression of basement membrane components in human endothelial cells cultured in high glucose. J Clin Invest 82: 735–738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Haneda M, Kikkawa R, Horide N et al. (1991) Glucose enhances type IV collagen production in cultured rat glomerular mesangial cells. Diabetologia 34: 198–200

    Article  CAS  PubMed  Google Scholar 

  9. Li W, Khatami M, Rockey J (1985) The effects of glucose and an aldose reductase inhibitor on the sorbitol content and collagen synthesis of bovine retinal pericytes in culture. Exp Eye Res 40: 439–444

    Article  CAS  PubMed  Google Scholar 

  10. Yorek MA, Dunlap JA, Ginsberg BH (1988) Effect of sorbinil on myo-inositol metabolism in cultured neuroblastoma cells exposed to increased glucose levels. J Neurochem 51: 331–338

    Article  CAS  PubMed  Google Scholar 

  11. Delmonte MA, Rabbani R, Diaz TC et al. (1991) Sorbitol, myo-inositol, and rod outer segment phagocytosis in cultured hRPE cells exposed to glucose. In vitro model of myo-inositol depletion. Hypothesis of diabetic complications. Diabetes 40: 1335–1345

    Article  CAS  Google Scholar 

  12. Fumo P, Kuncio GS, Ziyadeh FN (1994) PKC and high glucose stimulate collagen alpha 1 (IV) transcriptional activity in a reporter mesangial cell line. Am J Physiol 267:F632-F638

    CAS  PubMed  Google Scholar 

  13. Inoguchi T, Battan R, Handler E, Sportsman J, Heath W, King G (1992) Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats:differential reversibility to glycemic control by islet cell transplantation. Medical Sciences 89: 11059–11063

    CAS  Google Scholar 

  14. Ayo SH, Radnik RA, Glass II WF et al. (1991) Increased extracellular matrix synthesis and mRNA in mesangialeacells grown in high-glucose medium. Am J Physiol 260:F185-F191

    CAS  PubMed  Google Scholar 

  15. Studer R, Craven P, DeRubertis F (1993) Role for protein kinase C in the mediation of increased fibronectin accumulation by mesangial cells grown in high-glucose medium. Diabetes 42: 118–126

    Article  CAS  Google Scholar 

  16. Williams B, Schrier R (1992) Characterization of glucose-induced in situ protein kinase C activity in cultured vascular smooth muscle cells. Diabetes 41: 1464–1472

    Article  CAS  PubMed  Google Scholar 

  17. Tsilbary E, Charonis A, Reger L, Wohlhueter R, Furcht L (1988) The effect of non-enzymatic glucosylation on the binding of the main non-collagenous NC1 domain to type IV collagen. J Biol Chem 263: 4302–4308

    Google Scholar 

  18. Brownlee M (1992) Glycation products and the pathogenesis of diabetic complications. Diabetes Care 15: 1835–1843

    Article  CAS  PubMed  Google Scholar 

  19. Cohen MP, Ziyadeh FN (1994) Amadori glucose adducts modulate mesangial cell growth and collagen gene expression. Kidney Int 45: 475–484

    Article  CAS  PubMed  Google Scholar 

  20. Kassab JP, Guillot R, Andre J et al. (1994) Renal and microvascular effects of an aldose reductase inhibitor in experimental diabetes. Biochemical, functional and ultrastructural studies. Biochem Pharmacol 48: 1003–1008

    Article  CAS  PubMed  Google Scholar 

  21. Pugliese G, Pricci F, Pugliese F et al. (1994) Mechanisms of glucose-enhanced extracellular matrix accumulation in rat glomerular mesangial cells. Diabetes 43: 478–490

    Article  CAS  PubMed  Google Scholar 

  22. Bleyer AJ, Fumo P, Snipes ER, Goldfarb S, Simmons DA, Ziyadeh FN (1994) Polyol pathway mediates high glucose-induced collagen synthesis in proximal tubule. Kidney Int 45: 659–666

    Article  CAS  PubMed  Google Scholar 

  23. Jaffe E, Nacheman R, Becker C, Minick C (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Ivest 52: 2745–2756

    Article  CAS  Google Scholar 

  24. Jaffe E, Minick R, Adelman B, Becker C, Nachman R (1976) Synthesis of basement membrane collagen by cultured human endothelial cells. J Exp Med 144: 209–225

    Article  CAS  PubMed  Google Scholar 

  25. Kramer R, Fuh G, Karasek M (1985) Type IV collagen synthesis by cultured micro-vascular endothelial cells and its deposition into the subendothelial basement membrane. Biochemistry 24: 7423–7430

    Article  CAS  PubMed  Google Scholar 

  26. Peterkofsky B, Diegelman R (1971) Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins. Biochemistry 10: 988–994

    Article  CAS  PubMed  Google Scholar 

  27. Fiszer-Szafarz B, Szafarz D, De Murillo AG (1981) A general, fast, and sensitive micromethod for DNA determination: application to rat and mouse liver, rat hepatoma, human leukocytes, chicken fibroblasts, and yeast cells. Anal Biochem 110: 165–170

    Article  CAS  PubMed  Google Scholar 

  28. Hayakawa K, Walker L, Constable IJ (1990) The effect of glucose and insulin concentration on type IV collagen biosynthesis by bovine retinal capillary endothelial cells in vitro. Jpn J Ophthalmol 34: 463–471

    CAS  PubMed  Google Scholar 

  29. Ledbetter S, Copeland EJ (1990) Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. Diabetes 39: 196–203

    Article  CAS  PubMed  Google Scholar 

  30. Poulsom R, Kurkinen M, Prockop DJ, Boot-Handford RP (1988) Increased steady-state levels of laminin B1 mRNA in kidneys of long-term streptozotocin-diabetic rats. J Biol Chem 263: 10072–10076

    CAS  PubMed  Google Scholar 

  31. Hawthorne GC, Bartlett K, Hetherington CS, Alberti KGMM (1989) The effect of high glucose on polyol pathway activity and myo-inositol metabolism in cultured human endothelial cells. Diabetologia 32: 163–166

    Article  CAS  PubMed  Google Scholar 

  32. Koh MS, Misch KJ, Yucen CT, Rhodes EL (1986) Accumulation of sorbitol in endothelial cells:a possible cause of diabetic microangiopathy. Diabetes Res 3: 217–219

    CAS  PubMed  Google Scholar 

  33. Akagi Y, Kador PF, Kinoshita JH (1987) Immunohistochemical localization for aldose reductase in diabetic lenses. Invest Ophtalmol Visual Sci 28: 163–167

    CAS  Google Scholar 

  34. Das B, Srivastava SK (1985) Activation of aldose reductase from human tissues. Diabetes 34: 1145–1151

    Article  CAS  PubMed  Google Scholar 

  35. Dorin RI, Shah VO, Kaplan DL, Vela BS, Zager PG (1995) Regulation of aldose reductase gene expression in renal cortex and medulla of rats. Diabetologia 38: 46–54

    Article  CAS  PubMed  Google Scholar 

  36. Stevens MJ, Henry DN, Thomas TP, Kollen PD, Greene DA (1993) Aldose reductase gene expression and osmotic dysregulation in cultured human retinal pigment epithelial cells. Am J Physiol 265:E428-E438

    CAS  PubMed  Google Scholar 

  37. Dent MT, Tebbs SE, Gonzales AM, Ward JD, Wilson RM (1991) Neutrophil aldose reductase activity and its association with established diabetic microvascular complications. Diabet Med 8: 439–442

    Article  CAS  PubMed  Google Scholar 

  38. Shi S, Bekhor I (1994) Abnormal expression of aldose reductase mRNA in fiber cells of cataractous rat lens: analysis by in situ hybridization. Mol Cel Biochem 131: 35–41

    Article  CAS  Google Scholar 

  39. Nishimura C, Saito T, Ito T, Omori Y, Tanimoto T (1994) High levels of erythrocyte aldose reductase and diabetic retinopathy in NIDDM patients. Diabetologia 37: 328–330

    Article  CAS  PubMed  Google Scholar 

  40. Greene D, Lattimer S (1984) Action of sorbinil in diabetic periphral nerve: relationship of polyol (sorbitol) pathway inhibition to a myo-inositol mediated defect in sodium potassium ATPase activity. Diabetes 33: 712–716

    Article  CAS  PubMed  Google Scholar 

  41. Williamson JR, Chang K, Rowold E, et al. (1985) Sorbinil prevents diabetes-induced increases in vascular permeability but does not alter collagen cross-linking. Diabetes 34: 703–705

    Article  CAS  PubMed  Google Scholar 

  42. Yorek MA, Dunlap JA (1989) The effect of elevated glucose levels on myo-inositol metabolism in cultured bovine aortic endothelial cells. Metabolism 38: 16–22

    Article  CAS  PubMed  Google Scholar 

  43. Yorek MA, Dunlap JA, Stefani MR, Davidson EP (1994) Reduced Na+/K+ ATPase transport activity, resting membrane potential, and bradykinin-stimulated phos-phatidylinositol synthesis by polyol accumulation in cultured neuroblastoma cells. Neurochem Res 19: 321–329

    Article  CAS  PubMed  Google Scholar 

  44. Chatzilias AC, Whiteside CI (1994) Cellular mechanisms of glucose-induced myo-inositol transport upregulation in rat mesangial cells. Am J Physiol 267:F459-F466

    CAS  PubMed  Google Scholar 

  45. Das A, Franck R, Zhang N, Samadani E (1990) Increases in collagen type IV and laminin in galactose-induced retinal capillary basement membrane thickening. Prevention by an aldose reductase inhibitor. Exp Eye Res 50: 269–280

    Article  CAS  PubMed  Google Scholar 

  46. Bakillah A (1994) Production of type IV collagen and 72 kDa gelatinase by human endothelial cells cultured in the presence of various glucose concentrations and growth hormone. Effects of an aldose reductase inhibitor, sorbinil, and a protein kinase C inhibitor, GF109203X. René Descartes University, Paris [Thesis, in French]

    Google Scholar 

  47. Shiba T, Inoguchi T, Sportsman J, Heath W, Bursell S, King G (1993) Correlation of diacylglycerol level and protein kinase C activity in rat retina to retinal circulation. Am J Physiol 265:E783–E793

    CAS  PubMed  Google Scholar 

  48. Xia P, Inoguchi T, Kern TS, Engerman RL, Oates PJ, King GL (1994) Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes 43: 1122–1129

    Article  CAS  PubMed  Google Scholar 

  49. Craven P, De Rubertis F (1989) Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. Possible mediation by glucose. J Clin Invest 83: 1667–1675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Charonis AS, Reger LA, Dege JE, Kouzikoliakos K, Furcht LT, Wohlhueter RM, Tsilibary EC (1990) Laminin alterations after in vitro nonenzymatic glucosylation. Diabetes 39: 807–814

    Article  CAS  PubMed  Google Scholar 

  51. Cohen M, Klepser H, Wu V (1991) Evaluation of the effect of aldose reductase inhibition on increased basement membrane collagen fluorescence in diabetic rats. Gen Pharmacol 22: 603–606

    Article  CAS  PubMed  Google Scholar 

  52. Bunn HF, Higgins PJ (1981) Reaction of monosaccharides with proteins: possible evolutionary significance. Science 213: 222–224

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Equipe de Recherches sur la Biochimie et la Pharmacologie des Vaisseaux et du Rein, Faculté de Médecine Broussais-HÔtel-Dieu, U.F.R. Biomédicale des Saints-Pères, Université de Paris V & VI, Paris, France

    A. Bakillah, A. M. Grigorova-Borsos, R. Guillot, P. Urios & M. Sternberg

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  1. A. Bakillah
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  2. A. M. Grigorova-Borsos
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  3. R. Guillot
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  4. P. Urios
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  5. M. Sternberg
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Bakillah, A., Grigorova-Borsos, A.M., Guillot, R. et al. Effect of an aldose reductase inhibitor on type IV collagen production by human endothelial cells cultured in high glucose. Diabetologia 39, 641–648 (1996). https://doi.org/10.1007/BF00418535

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  • DOI: https://doi.org/10.1007/BF00418535

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