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Los productos finales de glicación (AGEs) son un grupo heterogéneo de moléculas generadas por medio de reacciones no enzimáticas de glicación y de oxidación de proteínas, lípidos y ácidos nucleicos. La formación aumentada de AGEs ocurre en condiciones tales como la diabetes mellitus y el envejecimiento. AGEs median sus efectos a través de tres mecanismos principales: 1) entrecruzamiento con proteínas de la matriz extracelular, afectando las propiedades mecánicas de los tejidos, 2) entrecruzamiento con proteínas intracelulares alterando sus funciones fisiológicas y 3) unión a sus receptores de superficie RAGE para inducir múltiples cascadas de señales intracelulares. La acumulación de AGEs en las proteínas tisulares ha sido implicada en las complicaciones vasculares diabéticas, tales como la retinopatía, la nefropatía y la neuropatía. En la nefropatía diabética los AGEs contribuyen al desarrollo y progresión de esta enfermedad renal.

Productos finales de glicosilación avanzada; Reacción de Maillard; Complicaciones de la diabetes; Membrana basal glomerular

Advanced glycation end products (AGEs) are a heterogenous group of molecules that are generated through nonenzimatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation and accumulation of AGEs has been reported to occur in conditions such as diabetes mellitus as well as in natural aging. AGEs mediate their effects through three main mechanism: 1) cross linking extracellular (matrix) proteins thereby affecting tissue mechanical properties, 2) cross linking intracellular proteins thus altering their physiological functios and 3) binding to their cell surface receptor RAGE to inducing multiple intracellular signalling cascades. The accumulation of AGEs in tissue proteins has been implicated in diabetic vascular complications, such as retinopathy, nephropathy and neuropathy. In the diabetic nephropathy AGEs contribute to the development and progression of this renal disease.

Glycosylation end products; advanced; Maillard reaction; Diabetes complications; Glomerular basement membrane

Carlos Carvajal Carvajal^*+

Key

Figura 1) (5,6). En las proteínas los AGE se forman sobre residuos de lisina o arginina predominantemente (7). Además de la reacción de Maillard otras vías pueden originar los AGE, como por ejemplo la autooxidación de la glucosa y la peroxidación de los lípidos que originan derivados dicarbonílicos a partir de un incremento del estrés oxidativo (8). Figura 1

Figura 1

Glicación

Figura 2

Figura 2

Referencias bibliográficas

1. Frye, E. B., Degenhardt, T. P., Thorpe, S. R. & Baynes, J. W. (1998). Role of Maillard reaction in aging of tissue proteins. Advanced glycation end product-dependent increase in imidazolium cross-links in human lens proteins. J Biol Chem, 273, 18714-18719.
2. Hegab, Z., Gibbons, S., Neyses, L. & Mamas, M. (2012). Role of advanced glycation end products in cardiovascular disease. World J Cardiology, 4, 4, 90-102.
3. Piarulli, F., Sartore, G. & Lapolla, A. (2013). Glyco-oxidation and cardiovascular complications in type 2 diabetes: a clinical update. Acta Diabetol, 50, 101- 110.
4. Watkins, N. G., Thorpe, S. R. & Baynes, J. W. (1985). Glycation of amino groups in protein. J Biol Chem, 260, 10629-10636.
5. Schalkwijk, C. & Miyata, T. (2012). Early- and advanced non-enzimatic glycation in diabetic vascular complications: the search for therapeutics. Amino Acids, 42, 1193-1204.
6. Taguchi, A., Blood, D. C., Del Toro, G. & Canet, A., et al. (2000). Blockade of RAGE-amphoterin signaling suppresses tomour growth and metastases. Nature, 405, 354-360.
7. Ramasamy, R., Yan, S. & Schmidt, A. (2012). Advanced glycation endproducts: from precursors to RAGE: round and round we go. Amino Acids, 42, 4, 1151-1161.
8. Luevano, C. & Chapman, K. (2010). Dietary advanced glycation end producti and aging. Nutrients, 2, 1247-1265.
9. Boon, P., Pun. L. & Murphy, M. (2012). Pathological significance of mitochondrial glycation. International J Cell Biology, 2012, 1-13.
11. Bornfeldt, K. & Tabas, I. (2011). Insulin resistance, hyperglycemia and atherosclerosis. Cell Metab, 2, 14, 575-585.
12. Yan, S., Chen, D., Yan S., Guo, L. & Chen, J. (2013). RAGE is a key cellular target for Aβ-induced perturbation in Alzheimer´disease, Front Biosci (Schol Ed), 4, 240-250.
et al. (2013). Glycation exacerbates the neuronal toxicity of β-amyloid. Cell Death and Disease, 4, 1-110
14. Deane, R., Singh, I., Sagare, A., Bell, R., Ross, N., La Rue, B., et al. (2012). A multimodel RAGE.specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. The Journal of Clinical Investigation, 122, 4, 1377-1392.
15. Yamagishi, S. I. & Matsui, T. (2010). Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxidative medicine and cellular longevity, 3, 2, 101-108.
16. Kolset, S., Reinholt, F. & Jenssen, T. (2012). Diabetic nephropathy and extracellular matrix. J Histochemistry & Cytochemistry, 60, 12, 976-986.
17. Garg, P. & Rabelink, T. (2011). Glomerular proteinuria: a complex interplay between unique players. Adv Chronic Kidney, 18, 4, 233-242.
18. Vinge, L., Lees, G., Nielsen, R., Clifford E., et al. (2010). The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney. Nephrol Dial Transplant, 25, 2458-2467.
19. Ramasamy, R., Yan, S. & Schmidt, A. (2012). The diverse ligand repertoire of the receptor advanced glycation endproducts & pathways to the complications of diabetes. Vascul Pharmacol, 57, 5-6, 160-167.
20. Tabit, C. (2012). Endothelial dysfunction in diabetes mellitus: molecular mechanism and clinic implications. Rev Endocr Metab Disord, 11, 1, 61-74.
21. Lim, A. & Tesch, G. (2012). Inflamation in diabetic nephropathy. Mediators of inflammation, 2012, 1-12.
22. Raimundo, M. & López, J. (2011). Metabolic Syndrome, chronic kidney disease and cardiovascular disease: a dynamic and life-threatening triad. Cardiology Research ad Practice, 2011, 1-16.
23. Brownlee, M. & Lecture, L. (1994). Glycation and diabetic complications. Diabetes, 43, 836-841.
24. Makita, Z., Radoff, S., Rayfield, E. J., Yang, Z., et al. (1991). Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med, 325, 836-842.
25. Gella, A. & Durany, N. (2009). Oxidative stress in Alzheimer disease. Cell Adhesion & Migration, 3, 1, 88-93.
26. Younessi, P. & Yoonessi, A. (2011). Advanced glycation end-products and products and their receptor-mediated roles: inflammation and oxidative stress. Iran J Med Sci, 36, 3, 1-10.
27. Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813-820.
28. Border, W. A. & Noble, N. A. (1994). Transforming growth factor beta in tissue fibrosis. N Engl J Med, 331,1286-1292.
29. Goldfarb, S. & Ziyadeh, F. (2001). TGF-β: a crucial component of the pathogenesis of diabetic nephropathy. Transac Am Clin Climatol Assoc, 112, 27-33.
30. Panee, J. (2012). Monocyte chemoattractant protein (MCP-1) in obesity and diabetes. Cytokine, 60, 1, 1-12.
31. Yamagishi, S., Inagaki, Y. & Okamoto, T. (2002). Amano S. Advanced glycation end product-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattracant protein-1 in human mesangial cells. J Biol Chem, 277, 20309-20315.
32. Reiniger, N., Lau, K., McCalla, D., Eby, B., Cheng, B., Lu, Y., et al. (2010). Deletion of the receptor for advanced glycation end products reduces glomerulosclerosis and preserves renal function in the diabetic OVE26 mouse. Diabetes, 59, 2043-2055.
33. I nagi, R., Yamamoto, Y., Nangaku, M. & Usuda, N. (2006). A severe diabetic nephropathy model with early development of nodule-like lesions induced by megsin overexpression in RAGE/iNOS transgenic mice. Diabetes, 55, 356- 366.
34. Forbes, J. M., Cooper, M. E., Thallas, V. & Burns, W. C. (2002). Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetic nephropathy. Diabetes, 51, 3274-3282.
35. Kanwar, Y. S., Sun, L., Xie, P. & Liu, F. Y. (2011). A glimpse of various pathogenetic mechanism of diabetic nephropathy. Annu Rev Patol, 6, 395- 423.

^* Microbiólogo. Especialista en Química Clínica. E-mail: ccarvajal313@yahoo.com

Recibido para publicación el 12 de agosto de 2014 Aceptado el 16 de setiembre de 2014

Fechas de Publicación

Publicación en esta colección
29 Mayo 2015
Fecha del número
Mar 2015

Histórico

Recibido
12 Ago 2014
Acepto
16 Set 2014

[1] 1. Frye, E. B., Degenhardt, T. P., Thorpe, S. R. & Baynes, J. W. (1998). Role of Maillard reaction in aging of tissue proteins. Advanced glycation end product-dependent increase in imidazolium cross-links in human lens proteins. J Biol Chem, 273, 18714-18719.

[2] 2. Hegab, Z., Gibbons, S., Neyses, L. & Mamas, M. (2012). Role of advanced glycation end products in cardiovascular disease. World J Cardiology, 4, 4, 90-102.

[3] 3. Piarulli, F., Sartore, G. & Lapolla, A. (2013). Glyco-oxidation and cardiovascular complications in type 2 diabetes: a clinical update. Acta Diabetol, 50, 101- 110.

[4] 4. Watkins, N. G., Thorpe, S. R. & Baynes, J. W. (1985). Glycation of amino groups in protein. J Biol Chem, 260, 10629-10636.

[5] 5. Schalkwijk, C. & Miyata, T. (2012). Early- and advanced non-enzimatic glycation in diabetic vascular complications: the search for therapeutics. Amino Acids, 42, 1193-1204.

[6] 6. Taguchi, A., Blood, D. C., Del Toro, G. & Canet, A., et al. (2000). Blockade of RAGE-amphoterin signaling suppresses tomour growth and metastases. Nature, 405, 354-360.

[7] 7. Ramasamy, R., Yan, S. & Schmidt, A. (2012). Advanced glycation endproducts: from precursors to RAGE: round and round we go. Amino Acids, 42, 4, 1151-1161.

[8] 8. Luevano, C. & Chapman, K. (2010). Dietary advanced glycation end producti and aging. Nutrients, 2, 1247-1265.

[9] 9. Boon, P., Pun. L. & Murphy, M. (2012). Pathological significance of mitochondrial glycation. International J Cell Biology, 2012, 1-13.

[11] 11. Bornfeldt, K. & Tabas, I. (2011). Insulin resistance, hyperglycemia and atherosclerosis. Cell Metab, 2, 14, 575-585.

[12] 12. Yan, S., Chen, D., Yan S., Guo, L. & Chen, J. (2013). RAGE is a key cellular target for Aβ-induced perturbation in Alzheimer´disease, Front Biosci (Schol Ed), 4, 240-250.

[13] et al. (2013). Glycation exacerbates the neuronal toxicity of β-amyloid. Cell Death and Disease, 4, 1-110

[14] 14. Deane, R., Singh, I., Sagare, A., Bell, R., Ross, N., La Rue, B., et al. (2012). A multimodel RAGE.specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. The Journal of Clinical Investigation, 122, 4, 1377-1392.

[15] 15. Yamagishi, S. I. & Matsui, T. (2010). Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxidative medicine and cellular longevity, 3, 2, 101-108.

[16] 16. Kolset, S., Reinholt, F. & Jenssen, T. (2012). Diabetic nephropathy and extracellular matrix. J Histochemistry & Cytochemistry, 60, 12, 976-986.

[17] 17. Garg, P. & Rabelink, T. (2011). Glomerular proteinuria: a complex interplay between unique players. Adv Chronic Kidney, 18, 4, 233-242.

[18] 18. Vinge, L., Lees, G., Nielsen, R., Clifford E., et al. (2010). The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney. Nephrol Dial Transplant, 25, 2458-2467.

[19] 19. Ramasamy, R., Yan, S. & Schmidt, A. (2012). The diverse ligand repertoire of the receptor advanced glycation endproducts & pathways to the complications of diabetes. Vascul Pharmacol, 57, 5-6, 160-167.

[20] 20. Tabit, C. (2012). Endothelial dysfunction in diabetes mellitus: molecular mechanism and clinic implications. Rev Endocr Metab Disord, 11, 1, 61-74.

[21] 21. Lim, A. & Tesch, G. (2012). Inflamation in diabetic nephropathy. Mediators of inflammation, 2012, 1-12.

[22] 22. Raimundo, M. & López, J. (2011). Metabolic Syndrome, chronic kidney disease and cardiovascular disease: a dynamic and life-threatening triad. Cardiology Research ad Practice, 2011, 1-16.

[23] 23. Brownlee, M. & Lecture, L. (1994). Glycation and diabetic complications. Diabetes, 43, 836-841.

[24] 24. Makita, Z., Radoff, S., Rayfield, E. J., Yang, Z., et al. (1991). Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med, 325, 836-842.

[25] 25. Gella, A. & Durany, N. (2009). Oxidative stress in Alzheimer disease. Cell Adhesion & Migration, 3, 1, 88-93.

[26] 26. Younessi, P. & Yoonessi, A. (2011). Advanced glycation end-products and products and their receptor-mediated roles: inflammation and oxidative stress. Iran J Med Sci, 36, 3, 1-10.

[27] 27. Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813-820.

[28] 28. Border, W. A. & Noble, N. A. (1994). Transforming growth factor beta in tissue fibrosis. N Engl J Med, 331,1286-1292.

[29] 29. Goldfarb, S. & Ziyadeh, F. (2001). TGF-β: a crucial component of the pathogenesis of diabetic nephropathy. Transac Am Clin Climatol Assoc, 112, 27-33.

[30] 30. Panee, J. (2012). Monocyte chemoattractant protein (MCP-1) in obesity and diabetes. Cytokine, 60, 1, 1-12.

[31] 31. Yamagishi, S., Inagaki, Y. & Okamoto, T. (2002). Amano S. Advanced glycation end product-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattracant protein-1 in human mesangial cells. J Biol Chem, 277, 20309-20315.

[32] 32. Reiniger, N., Lau, K., McCalla, D., Eby, B., Cheng, B., Lu, Y., et al. (2010). Deletion of the receptor for advanced glycation end products reduces glomerulosclerosis and preserves renal function in the diabetic OVE26 mouse. Diabetes, 59, 2043-2055.

[33] 33. I nagi, R., Yamamoto, Y., Nangaku, M. & Usuda, N. (2006). A severe diabetic nephropathy model with early development of nodule-like lesions induced by megsin overexpression in RAGE/iNOS transgenic mice. Diabetes, 55, 356- 366.

[34] 34. Forbes, J. M., Cooper, M. E., Thallas, V. & Burns, W. C. (2002). Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetic nephropathy. Diabetes, 51, 3274-3282.

[35] 35. Kanwar, Y. S., Sun, L., Xie, P. & Liu, F. Y. (2011). A glimpse of various pathogenetic mechanism of diabetic nephropathy. Annu Rev Patol, 6, 395- 423.

Productos finales de glicación (AGES) y la nefropatía diabética

Resúmenes

Referencias bibliográficas

Fechas de Publicación

Histórico