Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation

BMC Biochemistry - Tập 12 - Trang 1-13 - 2011
Luis MA Oliveira1,2,3, Ana Lages1, Ricardo A Gomes1,4, Henrique Neves1, Carlos Família1, Ana V Coelho4, Alexandre Quintas1
1Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior das Ciências da Saúde Egas Moniz, Caparica, Portugal
2Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Lisboa, Portugal
3Departamento de Análises Clínicas e Saúde Pública, Escola Superior de Saúde Dr. Lopes Dias, Instituto Politécnico de Castelo Branco, Castelo Branco, Portugal
4Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal

Tóm tắt

Insulin is a hormone that regulates blood glucose homeostasis and is a central protein in a medical condition termed insulin injection amyloidosis. It is intimately associated with glycaemia and is vulnerable to glycation by glucose and other highly reactive carbonyls like methylglyoxal, especially in diabetic conditions. Protein glycation is involved in structure and stability changes that impair protein functionality, and is associated with several human diseases, such as diabetes and neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Familiar Amyloidotic Polyneuropathy. In the present work, methylglyoxal was investigated for their effects on the structure, stability and fibril formation of insulin. Methylglyoxal was found to induce the formation of insulin native-like aggregates and reduce protein fibrillation by blocking the formation of the seeding nuclei. Equilibrium-unfolding experiments using chaotropic agents showed that glycated insulin has a small conformational stability and a weaker dependence on denaturant concentration (smaller m-value). Our observations suggest that methylglyoxal modification of insulin leads to a less compact and less stable structure that may be associated to an increased protein dynamics. We propose that higher dynamics in glycated insulin could prevent the formation of the rigid cross-β core structure found in amyloid fibrils, thereby contributing to the reduction in the ability to form fibrils and to the population of different aggregation pathways like the formation of native-like aggregates.

Tài liệu tham khảo

Shepherd PR, Kahn BB: Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus. N Engl J Med. 1999, 341 (4): 248-257. 10.1056/NEJM199907223410406.

Taylor R: Insulin action 1991. Clin Endocrinol (Oxf). 1991, 34 (2): 159-171. 10.1111/j.1365-2265.1991.tb00287.x.

Zierath JR, Krook A, Wallberg-Henriksson H: Insulin action and insulin resistance in human skeletal muscle. Diabetologia. 2000, 43 (7): 821-835. 10.1007/s001250051457.

Baker EN, Blundell TL, Cutfield JF, Cutfield SM, Dodson EJ, Dodson GG, Hodgkin DM, Hubbard RE, Isaacs NW, Reynolds CD, Sakabe K, Sakabe N, Vijayan NM: The structure of 2Zn pig insulin crystals at 1.5 A resolution. Philos Trans R Soc Lond B Biol Sci. 1988, 319 (1195): 369-456. 10.1098/rstb.1988.0058.

Blundell TL, Cutfield JF, Cutfield SM, Dodson EJ, Dodson GG, Hodgkin DC, Mercola DA: Three-dimensional atomic structure of insulin and its relationship to activity. Diabetes. 1972, 21 (2 Suppl): 492-505.

Nystrom FH, Quon MJ: Insulin signalling: metabolic pathways and mechanisms for specificity. Cell Signal. 1999, 11 (8): 563-574. 10.1016/S0898-6568(99)00025-X.

Ottensmeyer FP, Beniac DR, Luo RZ, Yip CC: Mechanism of transmembrane signaling: insulin binding and the insulin receptor. Biochemistry. 2000, 39 (40): 12103-12112. 10.1021/bi0015921.

Ahmad A, Uversky VN, Hong D, Fink AL: Early events in the fibrillation of monomeric insulin. J Biol Chem. 2005, 280 (52): 42669-42675. 10.1074/jbc.M504298200.

Brange J, Andersen L, Laursen ED, Meyn G, Rasmussen E: Toward understanding insulin fibrillation. J Pharm Sci. 1997, 86 (5): 517-525. 10.1021/js960297s.

Westermark P, Benson MD, Buxbaum JN, Cohen AS, Frangione B, Ikeda S, Masters CL, Merlini G, Saraiva MJ, Sipe JD: Amyloid: toward terminology clarification. Report from the Nomenclature Committee of the International Society of Amyloidosis. Amyloid. 2005, 12 (1): 1-4. 10.1080/13506120500032196.

Dische FE, Wernstedt C, Westermark GT, Westermark P, Pepys MB, Rennie JA, Gilbey SG, Watkins PJ: Insulin as an amyloid-fibril protein at sites of repeated insulin injections in a diabetic patient. Diabetologia. 1988, 31 (3): 158-161. 10.1007/BF00276849.

Storkel S, Schneider HM, Muntefering H, Kashiwagi S: Iatrogenic, insulin-dependent, local amyloidosis. Lab Invest. 1983, 48 (1): 108-111.

Wilhelm KR, Yanamandra K, Gruden MA, Zamotin V, Malisauskas M, Casaite V, Darinskas A, Forsgren L, Morozova-Roche LA: Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients. Eur J Neurol. 2007, 14 (3): 327-334.

Jimenez JL, Nettleton EJ, Bouchard M, Robinson CV, Dobson CM, Saibil HR: The protofilament structure of insulin amyloid fibrils. Proc Natl Acad Sci USA. 2002, 99 (14): 9196-9201. 10.1073/pnas.142459399.

Vestergaard B, Groenning M, Roessle M, Kastrup JS, van de Weert M, Flink JM, Frokjaer S, Gajhede M, Svergun DI: A helical structural nucleus is the primary elongating unit of insulin amyloid fibrils. PLoS Biol. 2007, 5 (5): e134-10.1371/journal.pbio.0050134.

Brownlee M: Biochemistry and molecular cell biology of diabetic complications. Nature. 2001, 414 (6865): 813-820. 10.1038/414813a.

Abdel-Wahab YH, O'Harte FP, Ratcliff H, McClenaghan NH, Barnett CR, Flatt PR: Glycation of insulin in the islets of Langerhans of normal and diabetic animals. Diabetes. 1996, 45 (11): 1489-1496. 10.2337/diabetes.45.11.1489.

Brownlee M: Advanced protein glycosylation in diabetes and aging. Annu Rev Med. 1995, 46: 223-234. 10.1146/annurev.med.46.1.223.

Lyons TJ, Silvestri G, Dunn JA, Dyer DG, Baynes JW: Role of glycation in modification of lens crystallins in diabetic and nondiabetic senile cataracts. Diabetes. 1991, 40 (8): 1010-1015. 10.2337/diabetes.40.8.1010.

Miyata T, Ueda Y, Saito A, Kurokawa K: 'Carbonyl stress' and dialysis-related amyloidosis. Nephrol Dial Transplant. 2000, 15 (Suppl 1): 25-28.

Kume S, Takeya M, Mori T, Araki N, Suzuki H, Horiuchi S, Kodama T, Miyauchi Y, Takahashi K: Immunohistochemical and ultrastructural detection of advanced glycation end products in atherosclerotic lesions of human aorta with a novel specific monoclonal antibody. Am J Pathol. 1995, 147 (3): 654-667.

Bucala R, Cerami A: Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol. 1992, 23: 1-34.

Vitek MP, Bhattacharya K, Glendening JM, Stopa E, Vlassara H, Bucala R, Manogue K, Cerami A: Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci USA. 1994, 91 (11): 4766-4770. 10.1073/pnas.91.11.4766.

Yan SD, Chen X, Schmidt AM, Brett J, Godman G, Zou YS, Scott CW, Caputo C, Frappier T, Smith MA, Perry G, Yen SH, Stern D: Glycated tau protein in Alzheimer's disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci USA. 1994, 91 (16): 7787-7791. 10.1073/pnas.91.16.7787.

Chen F, Wollmer MA, Hoerndli F, Munch G, Kuhla B, Rogaev EI, Tsolaki M, Papassotiropoulos A, Gotz J: Role for glyoxalase I in Alzheimer's disease. Proc Natl Acad Sci USA. 2004, 101 (20): 7687-7692. 10.1073/pnas.0402338101.

Castellani R, Smith MA, Richey PL, Perry G: Glycoxidation and oxidative stress in Parkinson disease and diffuse Lewy body disease. Brain Res. 1996, 737 (1-2): 195-200. 10.1016/0006-8993(96)00729-9.

Gomes R, Sousa Silva M, Quintas A, Cordeiro C, Freire A, Pereira P, Martins A, Monteiro E, Barroso E, Ponces Freire A: Argpyrimidine, a methylglyoxal-derived advanced glycation end-product in familial amyloidotic polyneuropathy. Biochem J. 2005, 385 (Pt 2): 339-345.

Richard JP: Mechanism for the formation of methylglyoxal from triosephosphates. Biochem Soc Trans. 1993, 21 (2): 549-553.

Chen K, Maley J, Yu PH: Potential inplications of endogenous aldehydes in beta-amyloid misfolding, oligomerization and fibrillogenesis. J Neurochem. 2006, 99 (5): 1413-1424. 10.1111/j.1471-4159.2006.04181.x.

Jia X, Olson DJ, Ross AR, Wu L: Structural and functional changes in human insulin induced by methylglyoxal. FASEB J. 2006, 20 (9): 1555-1557. 10.1096/fj.05-5478fje.

Gomes RA, Sousa Silva M, Vicente Miranda H, Ferreira AE, Cordeiro CA, Freire AP: Protein glycation in Saccharomyces cerevisiae. Argpyrimidine formation and methylglyoxal catabolism. FEBS J. 2005, 272 (17): 4521-4531. 10.1111/j.1742-4658.2005.04872.x.

Gomes RA, Oliveira LM, Silva M, Ascenso C, Quintas A, Costa G, Coelho AV, Sousa Silva M, Ferreira AE, Ponces Freire A, Cordeiro C: Protein glycation in vivo: functional and structural effects on yeast enolase. Biochem J. 2008, 416 (3): 317-326. 10.1042/BJ20080632.

O'Harte FP, Hojrup P, Barnett CR, Flatt PR: Identification of the site of glycation of human insulin. Peptides. 1996, 17 (8): 1323-1330. 10.1016/S0196-9781(96)00231-8.

Guedes S, Vitorino R, Domingues MR, Amado F, Domingues P: Mass spectrometry characterization of the glycation sites of bovine insulin by tandem mass spectrometry. J Am Soc Mass Spectrom. 2009, 20 (7): 1319-1326. 10.1016/j.jasms.2009.03.004.

Lo TW, Westwood ME, McLellan AC, Selwood T, Thornalley PJ: Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alpha-acetylcysteine, and N alpha-acetyllysine, and bovine serum albumin. J Biol Chem. 1994, 269 (51): 32299-32305.

Jarrett JT, Lansbury PT: Amyloid fibril formation requires a chemically discriminating nucleation event: studies of an amyloidogenic sequence from the bacterial protein OsmB. Biochemistry. 1992, 31 (49): 12345-12352. 10.1021/bi00164a008.

Jarrett JT, Lansbury PT: Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?. Cell. 1993, 73 (6): 1055-1058. 10.1016/0092-8674(93)90635-4.

Lomakin A, Teplow DB, Kirschner DA, Benedek GB: Kinetic theory of fibrillogenesis of amyloid beta-protein. Proc Natl Acad Sci USA. 1997, 94 (15): 7942-7947. 10.1073/pnas.94.15.7942.

Wood SJ, Wypych J, Steavenson S, Louis JC, Citron M, Biere AL: alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease. J Biol Chem. 1999, 274 (28): 19509-19512. 10.1074/jbc.274.28.19509.

Nielsen L, Frokjaer S, Brange J, Uversky VN, Fink AL: Probing the mechanism of insulin fibril formation with insulin mutants. Biochemistry. 2001, 40 (28): 8397-8409. 10.1021/bi0105983.

Munishkina LA, Ahmad A, Fink AL, Uversky VN: Guiding protein aggregation with macromolecular crowding. Biochemistry. 2008, 47 (34): 8993-9006. 10.1021/bi8008399.

Lashuel HA, Lansbury PT: Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins?. Q Rev Biophys. 2006, 39 (2): 167-201. 10.1017/S0033583506004422.

Chellan P, Nagaraj RH: Protein crosslinking by the Maillard reaction: dicarbonyl-derived imidazolium crosslinks in aging and diabetes. Arch Biochem Biophys. 1999, 368 (1): 98-104. 10.1006/abbi.1999.1291.

Verzijl N, DeGroot J, Ben ZC, Brau-Benjamin O, Maroudas A, Bank RA, Mizrahi J, Schalkwijk CG, Thorpe SR, Baynes JW, Bijlsma JW, Lafeber FP, Tekoppel JM: Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. 2002, 46 (1): 114-123. 10.1002/1529-0131(200201)46:1<114::AID-ART10025>3.0.CO;2-P.

Nagaraj RH, Shipanova IN, Faust FM: Protein cross-linking by the Maillard reaction. Isolation, characterization, and in vivo detection of a lysine-lysine cross-link derived from methylglyoxal. J Biol Chem. 1996, 271 (32): 19338-19345. 10.1074/jbc.271.32.19338.

Ahmed N, Thornalley PJ: Peptide mapping of human serum albumin modified minimally by methylglyoxal in vitro and in vivo. Ann N Y Acad Sci. 2005, 1043: 260-266. 10.1196/annals.1333.031.

Pace CN: Determination and analysis of urea and guanidine hydrochloride denaturation curves. Methods in enzymology. 1986, 131: 266-280.

Myers JK, Pace CN, Scholtz JM: Denaturant m values and heat capacity changes: relation to changes in accessible surface areas of protein unfolding. Protein Sci. 1995, 4 (10): 2138-2148. 10.1002/pro.5560041020.

Ledesma MD, Bonay P, Colaco C, Avila J: Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem. 1994, 269 (34): 21614-21619.

Loske C, Gerdemann A, Schepl W, Wycislo M, Schinzel R, Palm D, Riederer P, Munch G: Transition metal-mediated glycoxidation accelerates cross-linking of beta-amyloid peptide. Eur J Biochem. 2000, 267 (13): 4171-4178.

Smith MA, Taneda S, Richey PL, Miyata S, Yan SD, Stern D, Sayre LM, Monnier VM, Perry G: Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci USA. 1994, 91 (12): 5710-5714. 10.1073/pnas.91.12.5710.

Munch G, Luth HJ, Wong A, Arendt T, Hirsch E, Ravid R, Riederer P: Crosslinking of alpha-synuclein by advanced glycation endproducts--an early pathophysiological step in Lewy body formation?. J Chem Neuroanat. 2000, 20 (3-4): 253-257. 10.1016/S0891-0618(00)00096-X.

Hashimoto N, Naiki H, Gejyo F: Modification of beta 2-microglobulin with D-glucose or 3-deoxyglucosone inhibits A beta 2M amyloid fibril extension in vitro. Amyloid. 1999, 6 (4): 256-264. 10.3109/13506129909007337.

Lee D, Park CW, Paik SR, Choi KY: The modification of alpha-synuclein by dicarbonyl compounds inhibits its fibril-forming process. Biochim Biophys Acta. 2009, 1794 (3): 421-430.

Chen L, Wei Y, Wang X, He R: Ribosylation rapidly induces alpha-synuclein to form highly cytotoxic molten globules of advanced glycation end products. PLoS One. 2010, 5 (2): e9052.-

Ivanova MI, Sievers SA, Sawaya MR, Wall JS, Eisenberg D: Molecular basis for insulin fibril assembly. Proc Natl Acad Sci USA. 2009, 106 (45): 18990-18995. 10.1073/pnas.0910080106.

Caughey B, Lansbury PT: Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci. 2003, 26: 267-298. 10.1146/annurev.neuro.26.010302.081142.

Crowther DC, Kinghorn KJ, Miranda E, Page R, Curry JA, Duthie FA, Gubb DC, Lomas DA: Intraneuronal Abeta, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer's disease. Neuroscience. 2005, 132 (1): 123-135. 10.1016/j.neuroscience.2004.12.025.

Danzer KM, Haasen D, Karow AR, Moussaud S, Habeck M, Giese A, Kretzschmar H, Hengerer B, Kostka M: Different species of alpha-synuclein oligomers induce calcium influx and seeding. J Neurosci. 2007, 27 (34): 9220-9232. 10.1523/JNEUROSCI.2617-07.2007.

Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM: Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature. 2009, 457 (7233): 1128-1132. 10.1038/nature07761.

Bierhaus A, Stern DM, Nawroth PP: RAGE in inflammation: a new therapeutic target?. Curr Opin Investig Drugs. 2006, 7 (11): 985-991.

Maczurek A, Shanmugam K, Munch G: Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease. Ann N Y Acad Sci. 2008, 1126: 147-151. 10.1196/annals.1433.026.

Brange J: Galenics of insulin. The physicochemical and pharmaceutical aspects of insulin and insulin preparations. 1987, Berlin: Springer-Verlag

Groenning M, Frokjaer S, Vestergaard B: Formation mechanism of insulin fibrils and structural aspects of the insulin fibrillation process. Curr Protein Pept Sci. 2009, 10 (5): 509-528. 10.2174/138920309789352038.

Naiki H, Higuchi K, Hosokawa M, Takeda T: Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavin T1. Analytical biochemistry. 1989, 177 (2): 244-249. 10.1016/0003-2697(89)90046-8.

Naiki H, Higuchi K, Matsushima K, Shimada A, Chen WH, Hosokawa M, Takeda T: Fluorometric examination of tissue amyloid fibrils in murine senile amyloidosis: use of the fluorescent indicator, thioflavine T. Lab Invest. 1990, 62 (6): 768-773.

Wilson CM: Studies and critique of Amido Black 10B, Coomassie Blue R, and Fast Green FCF as stains for proteins after polyacrylamide gel electrophoresis. Analytical biochemistry. 1979, 96 (2): 263-278. 10.1016/0003-2697(79)90581-5.

Johnson WC: Analyzing protein circular dichroism spectra for accurate secondary structures. Proteins. 1999, 35 (3): 307-312. 10.1002/(SICI)1097-0134(19990515)35:3<307::AID-PROT4>3.0.CO;2-3.

Lobley A, Whitmore L, Wallace BA: DICHROWEB: an interactive website for the analysis of protein secondary structure from circular dichroism spectra. Bioinformatics (Oxford, England). 2002, 18 (1): 211-212. 10.1093/bioinformatics/18.1.211.

Whitmore L, Wallace BA: DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data. Nucleic acids research. 2004, W668-673. 32 Web Server

Bolen DW, Santoro MM: Unfolding free energy changes determined by the linear extrapolation method. 2. Incorporation of delta G degrees N-U values in a thermodynamic cycle. Biochemistry. 1988, 27 (21): 8069-8074. 10.1021/bi00421a015.

Santoro MM, Bolen DW: Unfolding free energy changes determined by the linear extrapolation method. 1. Unfolding of phenylmethanesulfonyl alpha-chymotrypsin using different denaturants. Biochemistry. 1988, 27 (21): 8063-8068. 10.1021/bi00421a014.

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