BACKGROUND: Advanced glycation end-products (AGEs) have been implicated in the pathogenesis of diabetic nephropathy, and aminoguanidine (AG) has been shown to decrease the accumulation of AGEs in the diabetic kidney. METHODS: This study investigates changes in AGE binding associated with diabetes in the rat kidney using in vitro and in vivo autoradiographic techniques. Male Sprague-Dawley rats were randomized into control and diabetic groups with and without AG treatment and were sacrificed after three weeks. Frozen kidney sections (20 microm) were incubated with [125I]-AGE-RNase or [125I]-AGE-BSA. To localize the AGE binding site, in vivo autoradiography was performed by injection of 15 microCi of [125I]-AGE-BSA into the abdominal aorta of the rat. RESULTS: Low-affinity binding sites specific for AGEs in the renal cortex (IC50 = 0.28 microm) were detected by in vitro autoradiography. There was a significant increase in [125I]-AGE binding in the diabetic kidney, which was prevented by AG treatment. Emulsion autoradiography revealed that binding was localized primarily to proximal tubules in the renal cortex. Renal AGE levels, as assessed by fluorescence or by radioimmunoassay, were increased after three weeks of diabetes. This increase was attenuated by AG therapy. CONCLUSIONS: AGE binding sites are present within the proximal tubules of the kidney and appear to be modulated by endogenous AGE levels. It remains to be determined if these binding sites represent receptors involved in clearance of AGEs or are linked to pathogenic pathways that lead to the development of diabetic nephropathy.
BACKGROUND: Advanced glycation end-products (AGEs) have been implicated in the pathogenesis of diabetic nephropathy, and aminoguanidine (AG) has been shown to decrease the accumulation of AGEs in the diabetic kidney. METHODS: This study investigates changes in AGE binding associated with diabetes in the rat kidney using in vitro and in vivo autoradiographic techniques. Male Sprague-Dawley rats were randomized into control and diabetic groups with and without AG treatment and were sacrificed after three weeks. Frozen kidney sections (20 microm) were incubated with [125I]-AGE-RNase or [125I]-AGE-BSA. To localize the AGE binding site, in vivo autoradiography was performed by injection of 15 microCi of [125I]-AGE-BSA into the abdominal aorta of the rat. RESULTS: Low-affinity binding sites specific for AGEs in the renal cortex (IC50 = 0.28 microm) were detected by in vitro autoradiography. There was a significant increase in [125I]-AGE binding in the diabetic kidney, which was prevented by AG treatment. Emulsion autoradiography revealed that binding was localized primarily to proximal tubules in the renal cortex. Renal AGE levels, as assessed by fluorescence or by radioimmunoassay, were increased after three weeks of diabetes. This increase was attenuated by AG therapy. CONCLUSIONS: AGE binding sites are present within the proximal tubules of the kidney and appear to be modulated by endogenous AGE levels. It remains to be determined if these binding sites represent receptors involved in clearance of AGEs or are linked to pathogenic pathways that lead to the development of diabetic nephropathy.
Authors: Fernando Magdaleno; Chuck Christopher Blajszczak; Claudia Lisette Charles-Niño; Alma Marlene Guadrón-Llanos; Alan Omar Vázquez-Álvarez; Alejandra Guillermina Miranda-Díaz; Natalia Nieto; María Cristina Islas-Carbajal; Ana Rosa Rincón-Sánchez Journal: Exp Ther Med Date: 2019-08-20 Impact factor: 2.447
Authors: M D Oldfield; L A Bach; J M Forbes; D Nikolic-Paterson; A McRobert; V Thallas; R C Atkins; T Osicka; G Jerums; M E Cooper Journal: J Clin Invest Date: 2001-12 Impact factor: 14.808
Authors: Daniel P K Ng; Charles L Hardy; Wendy C Burns; Evelyne E Muggli; Nicole Kerr; Jane McCausland; Daine Alcorn; Timothy E Adams; Jeffrey D Zajac; Richard G Larkins; Marjorie E Dunlop Journal: Endocrine Date: 2002-06 Impact factor: 3.633
Authors: B J Davis; J M Forbes; M C Thomas; G Jerums; W C Burns; H Kawachi; T J Allen; M E Cooper Journal: Diabetologia Date: 2003-11-29 Impact factor: 10.122