晚期糖基化终末产物(Ages)的临床病理机制及抑制Ages药物的研究
王真,李电东
(中国医学科学院 中国协和医科大学医药生物技术研究所，北京100050)
[摘要]在糖尿病病人体内以及衰老进程中晚期糖基化终末产物(AGEs)是不断积累的，其可以通过直接或间接的方式对机体产生病理作用。本文概述的主要内容为AGEs对各种组织或细胞包括心血管组织、肾脏、大脑和骨组织等的间接病理作用和机制、介导该作用的AGEs受体或其他结合蛋白，以及抑制AGEs形成和作用的药物如氨基胍等。
[关键词] 晚期糖基化终末产物(AGEs); AGEs受体; 氨基胍
Clinical Pathological Actions and Inhibitors of Advanced Glycation Endproducts
Wang Zhen,Li Dian Dong
, http://www.100md.com
( Institute of Medical Biotechnology,Peking Union Medical College,Chinese Academy of Medical Science , Beijing 100050 )
[Abstract] Advanced glycation endproducts ( AGEs ) always accumulate in diabetic patients and senile people, which can cause pathological actions to the whole body in direct and indirect way. What is reviewed in this article includes the indirect pathological actions and mechanism of AGEs to various tissues and cells , including cardiovascular tissue,kidney,brain and bones,etc.,the AGEs receptor and other AGEs binding proteins that mediates this action and inhibitors that inhibit the formation and action of AGEs .
, 百拇医药
[Key words] advanced glycation endproducts ( AGEs ); AGEs receptor; aminoguanidine
[作者简介] 王真(1975-)，女，博士研究生。主要从事衰老机理和微生物药学研究。联系电话：(010)63165289。
[参考文献]
[1] Angelika Bierhaus, Marion A, Hofmann, et al. AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus.I. The AGE concept. Cardiovascular Research , 1998, (37):586-600.
[2] Cerami A . Glucose as a mediator of aging. J Am Geriatri Soc, 1985, 33:626-634.
, 百拇医药
[3] Song X, Bao M M , Li D D . Advanced glycation in D-galactose induced mouse aging mode. Mech AGEing Dev, 1999, 108:241-253.
[4] Miyata T, Kawai R, Taketomi S, et al. Possible involvement of advanced glycation end products in bone resorption. Nephrol Dial Transplant, 1996, 11 (suppl 5):54-7.
[5] Quehenberger P, Greten J, v-Riedesel J, et al. Endothelin-1 is under the control of the transcription factors P50/65(NF-KB)and AP-1. Ann Hematol , 1995, 70:211.A53.
, 百拇医药
[6] Bierhaus A , Illmer T, Kasper M, et al. Advanced glycation endproducts mediated induction of tissue factor in cultured endothelial cells is dependent on RAGE. Circulation , 1997, 96:2262-71.
[7] Vlassara H, Fuh H, Donnelly T, et al. Advanced glycation endproducts promote adhension molecule–1(VCAM-1,ICAM-1)expression and atheroma formation in normal rabbits. Mol Med , 1995, 1:447-456.
[8] Yamagishi S, Fujimori H, Yonekura H, et al. Advanced glycation endproducts accelerate calcification in microvascular pericytes. Biochem Biophys Res Commun ,1999 , 258(2):353-7.
, http://www.100md.com
[9] Miyata T, Notoya K, Yoshida K, et al. Advanced glycation endproducts enhance osteoclast-induced bone resorption in cultured mouse unfractioned bone cells and in rats implants subcutaneously with devitalized bone particles. J Am Soc Nephrol , 1997, 8:260-270.
[10] Monnier VM, et al. Nonenzymatic glycosylation,the maillard reaction and the aging process. J Gerontol Biol Sci., 1990, 45:B105-11.
[11] Chih-wei Yang, Vlassara H, Emmanuei P.Peten, et al. Advanced glycation endproducts up-regulate gene expression found in diabetic glomerular disease. Proc.Natl.Acad.Sci., 1994, 91:9436-9440.
, http://www.100md.com
[12] Scivittaro , Ganz MB, Weiss MF, et al. AGEs induce oxidative stress and activate protein kinase C-beta(II) in neonatal mesangial cells. Am J Physiol Renal Physiol , 2000 , 278(4): F676-83 .
[13] Sasaki N , Fukatsu R, Tsuzuki K, et al. Advanced glycation end products in Alzheimer’s disease and other neurodegenerative disease. Am J Pathol , 1998, 153 : 1149-55.
[14] Munch G , Gerlach M, Sian J, et al. Advanced glycation end products in neurodegeneration:more than early markers of oxidative stress? Ann Neurol , 1998, 44 (3 suppl 1) : S85-8 .
, 百拇医药
[15] Lalla,Lamster, Schmidt et al. Accelerated non-enzymatoc glycation and oxidation occur in the presence of hyperglycemia. Annals of Periodontology, 1998, 3:14-19.
[16] William F.Owen, Jr,Fan Fan H, et al. β2-microglobulin modified with advanced glycation end products modulates collogen synthesis by human fibroblasts. Kidney International, 1998, 53:1365-1373.
[17] Kirstein M, Aston C, Hintz R, et al. Receptor-specific induction of insulin-like growth factor I(IGF-I) in human monocytes by advanced glycosylation endproducts-modified proteins. J Clin Invest , 1992, 90:439-46.
, http://www.100md.com
[18] Farhad Imani, Yasuhiro Horii, Helen Vlassara , et al. Advanced glycosylation endproduct-specific receptors on human and rat T-lymphocytes mediate synthesis of interferon γ;role in tissue remodeling . J Exp Med, 1993, 178:2165-2172.
[19] Segawa Y, Shirao Y, Yamagishi S, et al. Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy.A possible participation of advanced glycation end products in the development of the early phase of diabetic retinopathy. Ophthalmic Res, 1998, 30:333-9.
, http://www.100md.com
[20] S.D.Yan, D.Stern, A.M.Schmidt , et al. What is the RAGE? The receptor for advanced glycation endproducts(RAGE) and the dark side of glucose. European Journal of Clinical Investigation, 1997, 27:179-181.
[21] Colchestern U et al. Cell activation by glycated proteins, AGE receptors, receptor recognition factors and functional classification of AGEs. Cell Mol Biol (Noisy-le-grand), 1998, 44(7):1013-23.
[22] Schmidt A, Osamu Hori, Rong Cao, et al. A novel cellular receptor for advanced glycation endproducts .Diadetes , 1996, 45(suppl.3):S77-80.
, 百拇医药
[23] Hori O, Brett J, Slattery, et al. The receptor for advanced glycation endproducts (RAGE) is a cellular binding site for amphoterin.J Biol Chem, 1995, 270;25752-61.
[24] Yan S-D, Chen X, Fu J, et al. RAGE in Alzheimer’s disease:a receptor mediating amyloid-beta peptide-induced oxidant stress,neurotoxicity,and activation of microglia. Nature, 1996, 383:685-91.
[25] Li YM, Mitsuhashi T, Wojciechowicz D, et al. Molecular identity and celluar distribution of advanced glycation endproducts receptors :relationship of p60 to OST-48 and p90 to 80K-H membrane proteins.Proc.Natl.Acad.Sci., 1996, 93(20):11047-52.
, 百拇医药
[26] Van Heyningen R , Harding JJ , et al. Do aspirin-like analgesics protect against cataract?A case-control study. Lancet, 1986, 1:1111-3.
[27] Corman B, Duriez M, Poitevin P , et al. Aminoguanidine prevents AGEs-related arterial stiffening and cardiac hypertropy. Proc.Natl.Acad.Sci., 1998, 95:1301-6.
[28] Kempe HP，Englemann K, Hasslaher Ch, et al. Effect of aminoguanidine in degradation of glomerular basement membrane. Diabetologia, 1989, 32:A502.
, 百拇医药
[29] Lewis BS , Harding JJ, et al. The effects of aminoguanidine on the glycation(nonenzymic glycosylation) of lens proteins. Exp Eye Res , 1990, 50:463-7.
[30] Nakamura S, Makita Z, Ishikawa S, et al. Progression of nephropathy in spontaneous diabetic rats is prevented by OPB-9195,a novel inhibitor of advanced glycation.Diabetes , 1997, 46:895-899.
[31] Giardino I, Edelstein D, Brownlee M, et al. BCL-2 expression or anti-oxiants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells. J Clin Invest, 1996, 97:1422-8.
[32] C .Renard, O.Chappey, M.-P.Wautier, et al. Recombinant advanced glycation end product receptor pharmacokinetics in normal and diabetic rats. Molecular Pharmacology, 1997, 52:54-62., http://www.100md.com
(中国医学科学院 中国协和医科大学医药生物技术研究所，北京100050)
[摘要]在糖尿病病人体内以及衰老进程中晚期糖基化终末产物(AGEs)是不断积累的，其可以通过直接或间接的方式对机体产生病理作用。本文概述的主要内容为AGEs对各种组织或细胞包括心血管组织、肾脏、大脑和骨组织等的间接病理作用和机制、介导该作用的AGEs受体或其他结合蛋白，以及抑制AGEs形成和作用的药物如氨基胍等。
[关键词] 晚期糖基化终末产物(AGEs); AGEs受体; 氨基胍
Clinical Pathological Actions and Inhibitors of Advanced Glycation Endproducts
Wang Zhen,Li Dian Dong
, http://www.100md.com
( Institute of Medical Biotechnology,Peking Union Medical College,Chinese Academy of Medical Science , Beijing 100050 )
[Abstract] Advanced glycation endproducts ( AGEs ) always accumulate in diabetic patients and senile people, which can cause pathological actions to the whole body in direct and indirect way. What is reviewed in this article includes the indirect pathological actions and mechanism of AGEs to various tissues and cells , including cardiovascular tissue,kidney,brain and bones,etc.,the AGEs receptor and other AGEs binding proteins that mediates this action and inhibitors that inhibit the formation and action of AGEs .
, 百拇医药
[Key words] advanced glycation endproducts ( AGEs ); AGEs receptor; aminoguanidine
[作者简介] 王真(1975-)，女，博士研究生。主要从事衰老机理和微生物药学研究。联系电话：(010)63165289。
[参考文献]
[1] Angelika Bierhaus, Marion A, Hofmann, et al. AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus.I. The AGE concept. Cardiovascular Research , 1998, (37):586-600.
[2] Cerami A . Glucose as a mediator of aging. J Am Geriatri Soc, 1985, 33:626-634.
, 百拇医药
[3] Song X, Bao M M , Li D D . Advanced glycation in D-galactose induced mouse aging mode. Mech AGEing Dev, 1999, 108:241-253.
[4] Miyata T, Kawai R, Taketomi S, et al. Possible involvement of advanced glycation end products in bone resorption. Nephrol Dial Transplant, 1996, 11 (suppl 5):54-7.
[5] Quehenberger P, Greten J, v-Riedesel J, et al. Endothelin-1 is under the control of the transcription factors P50/65(NF-KB)and AP-1. Ann Hematol , 1995, 70:211.A53.
, 百拇医药
[6] Bierhaus A , Illmer T, Kasper M, et al. Advanced glycation endproducts mediated induction of tissue factor in cultured endothelial cells is dependent on RAGE. Circulation , 1997, 96:2262-71.
[7] Vlassara H, Fuh H, Donnelly T, et al. Advanced glycation endproducts promote adhension molecule–1(VCAM-1,ICAM-1)expression and atheroma formation in normal rabbits. Mol Med , 1995, 1:447-456.
[8] Yamagishi S, Fujimori H, Yonekura H, et al. Advanced glycation endproducts accelerate calcification in microvascular pericytes. Biochem Biophys Res Commun ,1999 , 258(2):353-7.
, http://www.100md.com
[9] Miyata T, Notoya K, Yoshida K, et al. Advanced glycation endproducts enhance osteoclast-induced bone resorption in cultured mouse unfractioned bone cells and in rats implants subcutaneously with devitalized bone particles. J Am Soc Nephrol , 1997, 8:260-270.
[10] Monnier VM, et al. Nonenzymatic glycosylation,the maillard reaction and the aging process. J Gerontol Biol Sci., 1990, 45:B105-11.
[11] Chih-wei Yang, Vlassara H, Emmanuei P.Peten, et al. Advanced glycation endproducts up-regulate gene expression found in diabetic glomerular disease. Proc.Natl.Acad.Sci., 1994, 91:9436-9440.
, http://www.100md.com
[12] Scivittaro , Ganz MB, Weiss MF, et al. AGEs induce oxidative stress and activate protein kinase C-beta(II) in neonatal mesangial cells. Am J Physiol Renal Physiol , 2000 , 278(4): F676-83 .
[13] Sasaki N , Fukatsu R, Tsuzuki K, et al. Advanced glycation end products in Alzheimer’s disease and other neurodegenerative disease. Am J Pathol , 1998, 153 : 1149-55.
[14] Munch G , Gerlach M, Sian J, et al. Advanced glycation end products in neurodegeneration:more than early markers of oxidative stress? Ann Neurol , 1998, 44 (3 suppl 1) : S85-8 .
, 百拇医药
[15] Lalla,Lamster, Schmidt et al. Accelerated non-enzymatoc glycation and oxidation occur in the presence of hyperglycemia. Annals of Periodontology, 1998, 3:14-19.
[16] William F.Owen, Jr,Fan Fan H, et al. β2-microglobulin modified with advanced glycation end products modulates collogen synthesis by human fibroblasts. Kidney International, 1998, 53:1365-1373.
[17] Kirstein M, Aston C, Hintz R, et al. Receptor-specific induction of insulin-like growth factor I(IGF-I) in human monocytes by advanced glycosylation endproducts-modified proteins. J Clin Invest , 1992, 90:439-46.
, http://www.100md.com
[18] Farhad Imani, Yasuhiro Horii, Helen Vlassara , et al. Advanced glycosylation endproduct-specific receptors on human and rat T-lymphocytes mediate synthesis of interferon γ;role in tissue remodeling . J Exp Med, 1993, 178:2165-2172.
[19] Segawa Y, Shirao Y, Yamagishi S, et al. Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy.A possible participation of advanced glycation end products in the development of the early phase of diabetic retinopathy. Ophthalmic Res, 1998, 30:333-9.
, http://www.100md.com
[20] S.D.Yan, D.Stern, A.M.Schmidt , et al. What is the RAGE? The receptor for advanced glycation endproducts(RAGE) and the dark side of glucose. European Journal of Clinical Investigation, 1997, 27:179-181.
[21] Colchestern U et al. Cell activation by glycated proteins, AGE receptors, receptor recognition factors and functional classification of AGEs. Cell Mol Biol (Noisy-le-grand), 1998, 44(7):1013-23.
[22] Schmidt A, Osamu Hori, Rong Cao, et al. A novel cellular receptor for advanced glycation endproducts .Diadetes , 1996, 45(suppl.3):S77-80.
, 百拇医药
[23] Hori O, Brett J, Slattery, et al. The receptor for advanced glycation endproducts (RAGE) is a cellular binding site for amphoterin.J Biol Chem, 1995, 270;25752-61.
[24] Yan S-D, Chen X, Fu J, et al. RAGE in Alzheimer’s disease:a receptor mediating amyloid-beta peptide-induced oxidant stress,neurotoxicity,and activation of microglia. Nature, 1996, 383:685-91.
[25] Li YM, Mitsuhashi T, Wojciechowicz D, et al. Molecular identity and celluar distribution of advanced glycation endproducts receptors :relationship of p60 to OST-48 and p90 to 80K-H membrane proteins.Proc.Natl.Acad.Sci., 1996, 93(20):11047-52.
, 百拇医药
[26] Van Heyningen R , Harding JJ , et al. Do aspirin-like analgesics protect against cataract?A case-control study. Lancet, 1986, 1:1111-3.
[27] Corman B, Duriez M, Poitevin P , et al. Aminoguanidine prevents AGEs-related arterial stiffening and cardiac hypertropy. Proc.Natl.Acad.Sci., 1998, 95:1301-6.
[28] Kempe HP，Englemann K, Hasslaher Ch, et al. Effect of aminoguanidine in degradation of glomerular basement membrane. Diabetologia, 1989, 32:A502.
, 百拇医药
[29] Lewis BS , Harding JJ, et al. The effects of aminoguanidine on the glycation(nonenzymic glycosylation) of lens proteins. Exp Eye Res , 1990, 50:463-7.
[30] Nakamura S, Makita Z, Ishikawa S, et al. Progression of nephropathy in spontaneous diabetic rats is prevented by OPB-9195,a novel inhibitor of advanced glycation.Diabetes , 1997, 46:895-899.
[31] Giardino I, Edelstein D, Brownlee M, et al. BCL-2 expression or anti-oxiants prevent hyperglycemia-induced formation of intracellular advanced glycation endproducts in bovine endothelial cells. J Clin Invest, 1996, 97:1422-8.
[32] C .Renard, O.Chappey, M.-P.Wautier, et al. Recombinant advanced glycation end product receptor pharmacokinetics in normal and diabetic rats. Molecular Pharmacology, 1997, 52:54-62., http://www.100md.com