Summary
We examined the effect of glucose on aldose reductase mRNA expression and its activity in calf pulmonary artery endothelial cells. After the cells were exposed to 18 mmol/l glucose, aldose reductase mRNA expression began to increase at 6 h, reached a maximum (about 2.4-fold increase) at 12 h, and thereafter gradually decreased. Aldose reductase activity was found to strongly correlate with aldose reductase mRNA expression after cells were exposed to 18 mmol/l glucose. In contrast, aldose reductase mRNA expression was significantly decreased following exposure to 55 mmol/l glucose. Aldose reductase activity was also decreased at 24 h after 55 mmol/l glucose. The increase in aldose reductase mRNA level caused by glucose was inhibited by 1 μg/ml of actinomycin D. These phenomena appear to be glucose-specific since neither 3-O-methylglucose nor fructose affected the levels of aldose reductase mRNA. We clearly demonstrate that aldose reductase mRNA level and its activity are modulated by glucose in calf pulmonary artery endothelial cells. Our data suggest that activation of aldose reductase in endothelial cells may contribute to the development of diabetic macroangiopathy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ross R (1986) The pathogenesis of atherosclerosis. N Engl J Med 314: 488–500
Ross R, Glomset JA (1976) The pathogenesis of atherosclerosis. N Engl J Med 295: 369–377
Gabbay KH (1973) The sorbitol pathway and the complications of diabetes. N Engl J Med 288: 831–836
Kennedy A, Frank RN, Verma SD (1983) Aldose reductase activity in retinal and cerebral microvessels and cultured vascular cells. Invest Ophthalmol Vis Sci 24: 1250–1258
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
Ghahary A, Luo J, Gong Y et al. (1989) Increased renal aldose reductase activity, immunoreactivity, and mRNA in streptozotocin-induced diabetic rats. Diabetes 38: 1067–1071
Bekhor I, Shi S, Unakar NJ (1990) Management of aldose reductase mRNA abundance in rat lens undergoing reversal of galactose induced cataracts. A model for gene response to changes in the environment. Mol Cell Biochem 95: 55–60
Deborah C, Kaneko M, Stark H et al. (1990) Increase in aldose reductase mRNA in dog lens epithelial cells under hypertonic conditions. Exp Eye Res 50: 743–749
Chelly J, Kaplan JC, Maire P Gautron S, Kahn A (1988) Transcription of the dystrophin gene in human muscle and non muscle tissue. Nature 333: 858–860
Wang AM, Doyle MV, Mark DF (1989) Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci USA 86: 9717–9721
Maniatis T, Fritsch EF, Sambrook J, Nina I (1982) Extraction, purification, and analysis of messenger RNA from eukaryotic cells. In: Nancy F, Chris N, Michele F (eds) Molecular cloning: a laboratory manual. Cold Spring Harbor Lab., Cold Spring Harbor, pp 7.19–7.22
Buell GN, Wickens MP, Payvar F, Schimeke RT (1978) Synthesis of full length cDNAs from four partially purified oviduct mRNAs. J Biol Chem 253: 2471–2482
Petrash JM, Fanvello AD (1989) Isolation and characterization of cDNA clones encoding aldose reductase. Curr Eye Res 8: 1021–1027
Nudel U, Zakut R, Shani M, Neuman S, Levy Z, Yaffe D (1983) The nucleotide sequence of the rat cytoplasmic β-actin gene. Nucl Acids Res 11: 1159–1171
Dufrane SP, Malaisse WJ, Sener A (1984) A micromethod for the assay of aldose reductase, its application to pancreatic islet. Biochem Med 32: 99–105
Gyllensten UB, Erlich HA (1988) Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci USA 85: 7652–7656
Brownlee M, Vlassara H, Cerami A (1984) Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med 101: 527–537
Sagel J, Colwell JA, Crook L, Laimins M (1975) Increased platelet aggregation in early diabetes mellitus. Ann Intern Med 82: 733–738
Mustard JF, Packham MA (1984) Platelets and diabetes mellitus. N Engl J Med 311: 665–667
Schonfeld G (1985) Diabetes, lipoproteins, and atherosclerosis. Metabolism 34: 45–50
Yamauchi T, Ohnaka K, Takayanagi R, Umeda F, Nawata H (1990) Enhanced secretion of endothelin-1 by elevated glucose levels from cultured bovine aortic endothelial cells. FEBS Lett 267: 16–18
Chylak LT, Kinoshita JH (1969) A biochemical evaluation of a cataract induced in a high glucose medium. Invest Ophthalmol Vis Sci 8: 401–402
Greene DA, Lattimer SA, Sima AAF (1987) Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med 316: 599–606
Burg MB, Kador PF (1988) Sorbitol, osmoregulation, and the complications of diabetes. J Clin Invest 81: 635–640
Morrison AD, Clements RS Jr, Winegrad AI (1972) Effects of elevated glucose concentrations on the metabolism of the aortic wall. J Clin Invest 51: 3114–3123
Aida K, Tawata M, Shindo H, Onaya T (1990) Clinical significance of erythrocyte sorbitol-blood glucose ratios in type 2 diabetes mellitus. Diabetes Care 13: 461–467
Bondy C, Cowley BD, Lightman SL Jr, Kador PF (1990) Feed-back inhibition of aldose reductase gene expression in rat renal medulla. J Clin Invest 86: 1103–1108
Lorenzi M, Cagliero E, Toledo S (1985) Glucose toxicity for human endothelial cells in culture: delayed replication, disturbed cell cycle, and accelerated death. Diabetes 34: 621–627
Lorenzi M, Montisano D, Toledo S, Barrieux A (1986) High glucose induces DNA damage in cultured human endothelial cells. J Clin Invest 77: 322–325
Capetandes A, Gerritsen ME (1986) The effects of elevated glucose concentration on cultured bovine retinal endothelial (BRE) cells. Fed Proc 45: 460 (Abstract)
McPherson JD, Shilton BH, Walton DJ (1988) Role of fructose in glycation and cross-linking of proteins. Biochemistry 27: 1901–1907
Oimomi M, Sakai M, Ohara T et al. (1989) Acceleration of fructose mediated collagen glycation. J Int Med Res 17: 249–253
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ohtaka, M., Tawata, M., Hosaka, Y. et al. Glucose modulation of aldose reductase mRNA expression and its activity in cultured calf pulmonary artery endothelial cells. Diabetologia 35, 730–734 (1992). https://doi.org/10.1007/BF00429092
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00429092