Nonenzymatic glycation of peripheral and central nervous system proteins in experimental diabetes mellitus
Catherine Ryle PhD
Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
Department of Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom
Search for more papers by this authorC.K. Leow FRCS
Nuffield Department of Surgery, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
Search for more papers by this authorCorresponding Author
Michael Donaghy FRCP
Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
Department of Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom
Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom; Department of Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, United KingdomSearch for more papers by this authorCatherine Ryle PhD
Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
Department of Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom
Search for more papers by this authorC.K. Leow FRCS
Nuffield Department of Surgery, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
Search for more papers by this authorCorresponding Author
Michael Donaghy FRCP
Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
Department of Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom
Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom; Department of Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, United KingdomSearch for more papers by this authorAbstract
Nonenzymatic glycation of neural proteins could underlie diabetic peripheral neuropathy. Cytoskeletal and myelin protein fractions of central nervous system and peripheral nervous system (PNS) tissue from rats with streptozotocin-induced diabetes of 1.5 and 8 months duration were analyzed for glycation products. In sciatic nerve cytoskeletal preparations from both diabetic and control animals we found high levels of the early glycation product (measured as furosine) after 6 weeks, which had fallen markedly by 8 months. Conversely the advanced glycation end product (AGE), pentosidine, was low at 6 weeks and high by 8 months in diabetic animals. The levels of glycation products were much lower in spinal cord and spinal nerve from diabetic animals. There was increased borotritride labeling of neurofilament subunits, and of cross-linked material, in cytoskeletal fractions of diabetic sciatic nerves. These results show that the PNS cytoskeleton is vulnerable to nonenzymatic glycation, resulting in AGE formation, in diabetic rats and to a lesser extent in normals. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 577–584, 1997.
References
- 1 Bailey AJ, Sims TJ, Avery NC, Halligan EP: Non-enzymatic glycation of fibrous collagen: reaction products of glucose and ribose. Biochem J 1995; 305: 385–390.
- 2 Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.
- 3 Brown MJ, Sumner AJ, Greene DA, Diamond SM, Asbury AK: Distal neuropathy in experimental diabetes mellitus. Ann Neurol 1980; 8: 168–178.
- 4 Chiu FC, Norton WT: Bulk preparation of CNS cytoskeleton and the separation of individual neurofilament proteins by gel filtration: dye-binding characteristics and amino acid compositions. J Neurochem 1982; 39: 1252–1260.
- 5 Cullum NA, Mahon J, Stringer K, McLean WG: Glycation of rat sciatic nerve tubulin in experimental diabetes mellitus. Diabetologia 1991; 34: 387–389.
- 6 Dunn JA, Patrick JS, Thorpe SR, Baynes JW: Oxidation of glycated proteins: age-dependent accumulation of Nε-(carboxymethyl)lysine in lens protein. Biochemistry 1989; 28: 9464–9468.
- 7 Dunn JA, McCance DR, Thorpe SR, Lyons TJ, Baynes JW: Age-dependent accumulation of Nε-(carboxymethyl)-hydroxylysine in human skin collagen. Biochemistry 1991; 30: 1205–1210.
- 8 Dyck PJ, Lais A, Karnes JL, O'Brien P, Rizza R: Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy. Ann Neurol 1986; 19: 425–439.
- 9 Dyck PJ, Zimmerman BR, Vilen TH, Minnerath SR, Karnes JI, Yao JK, Poduslo JF: Nerve glucose, fructose, sorbitol, myoinositol and fibre degeneration and regeneration in diabetic neuropathy. N Engl J Med 1988; 319: 542–548.
- 10 Dyck PJ: Hypoxic neuropathy. Does hypoxia play a role in diabetic neuropathy? The 1988 Robert Wartenberg Lecture. Neurology 1989; 39: 111–118.
- 11 Greene DA, Latimer SA, Sima AAF: Sorbitol, phosphoinositides and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med 1987; 316: 599–606.
- 12 Hisanga S, Hirokawa N: The effects of dephosphorylation on the structure of the projections of neurofilament. J Neurosci 1989; 9: 959–966.
- 13 Hisanga S, Hirokawa N: Dephosphorylation-induced interactions of neurofilaments with microtubules. J Biol Chem 1990; 35: 21852–21858.
- 14 Hoffman PN, Griffin JW, Price DL: Control of axonal caliber by neurofilament transport. J Cell Biol 1984; 99: 705–714.
- 15 Johnson PC, Doll DC, Cromey DW: Pathogenesis of diabetic neuropathy. Ann Neurol 1986; 19: 450–457.
- 16 Lewis SE, Nixon RA: Multiple phosphorylated variants of the high molecular mass subunit of neurofilaments in axons of retinal cell neurons: characterisation and evidence for their differential association with stationary and moving neurofilaments. J Cell Biol 1988; 107: 2689–2701.
- 17
Lyons TJ,
Thorpe SR,
Baynes JW:
Glycation and autoxidation of proteins in aging and diabetes, in
N Ruderman,
J Williamson,
M Brownlee (eds):
Hyperglycaemia, Diabetes and Vascular Disease.
New York, Oxford, Oxford University Press,
1992,
pp 197–217.
10.1007/978-1-4614-7524-8_11 Google Scholar
- 18 Macioce P, Filliatreau G, Figliomeni B, Hassig R, Thiery J, Di Giamberardino L: Slow axonal transport impairment of cytoskeletal proteins in streptozotocin-induced diabetic neuropathy. J Neurochem 1989; 53: 1261–1267.
- 19 McLean WG, Pekiner C, Cullum NA, Casson IF: Post-translational modifications of nerve cytoskeletal proteins in experimental diabetes. Mol Neurobiol 1992; 6: 225–237.
- 20 Makita Z, Radoff S, Rayfield E, Yang Z, Skolnik E, Delaney V, Friedman EA, Cerami A, Vlassara H: Advanced glycosylation endproducts in patients with diabetic nephropathy. N Engl J Med 1991; 325: 836–842.
- 21 Medori R, Autiolio-Gambetti L, Jenich H, Gambetti P: Changes in axon size and slow axonal transport are related in experimental diabetic neuropathy. Neurology 1988; 38: 597–601.
- 22 Mohamed MA, Lerro KA, Prestwich GD: Polyacrylamide gel miniaturization improves protein visualization and autoradiographic detection. Anal Biochem 1989; 177: 287–290.
- 23 Monnier VM, Kohn RR, Cerami A: Accelerated age-related browning of human collagen in diabetes mellitus. Proc Natl Acad Sci USA 1984; 81: 583–587.
- 24 Monnier VM, Sell DR, Najaraj RH, Miyata S, Grandlee S, Odetti P, Ibrahim SA: Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging and uremia. Diabetes 1992; 41(suppl 2): 36–41.
- 25 Nixon RA: Axonal transport of cytoskeletal proteins, in RD Burgoyne (ed): Neuronal Cytoskeleton. New York, Wiley-Liss, 1991, pp 283–307.
- 26 Patel N, Llewelyn JG, Wright DW, Thomas PK: Glucose and leucine uptake by rat dorsal root ganglia is not insulin sensitive. J Neurol Sci 1994; 121: 159–162.
- 27 Ryle C, Donaghy M: Non-enzymatic glycation of peripheral nerve proteins in human diabetics. J Neurol Sci 1995; 129: 62–68.
- 28 Schmidt AM, Hori O, Brett J, Yan S-D, Wautier J-L, Stern D: Cellular receptors for advanced glycation endproducts. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler Thromb 1994; 14: 1521–1528.
- 29 Sell DR, Lapolla A, Odetti P, Fogarty J, Monnier VM: Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM. Diabetes 1992; 41: 1286–1292.
- 30 Sidenius P, Jakobsen J: Retrograde axonal transport. Diabetologia 1981; 20: 110–112.
- 31 Sternberger LA, Sternberger NH: Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci USA 1983; 80: 6126–6130.
- 32 Trüeb B, Fluckiger R, Winterhalter KH: Nonenzymatic glycosylation of basement membrane collagen in diabetes mellitus. Collagen Rel Res 1984; 4: 239–251.
- 33 Vitadello M, Filliatreau G, Dupont JL, Hassig R, Gorio A, Di Giamberardino L: Altered axonal transport of cytoskeletal proteins in the mutant diabetic mouse. J Neurochem 1985; 45: 860–868.
- 34 Vlassara H, Brownlee M, Cerami A: Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus. Proc Natl Acad Sci USA 1981; 78: 5190–5192.
- 35 Vlassara H, Brownlee M, Cerami A: Excessive nonenzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats. Diabetes 1983; 32: 670–674.
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