AIM: The goal of this work is to understand the cellular effects of advanced glycation end product (AGE)-modified protein on renal proximal tubule cells. BACKGROUND: A major function of the proximal tubule is to reabsorb and process filtered proteins. Diabetes is characterized by increased quantities of tissue and circulating proteins modified by AGEs. Therefore in diabetes, plasma proteins filtered at the glomerulus and presented to the renal proximal tubule are likely to be highly modified by AGEs. METHODS: The model system was electrically resistant polarized renal proximal tubular epithelial cells in monolayer culture. The model proteins comprise a well-characterized AGE, methylglyoxal-modified bovine serum albumin (MGO-BSA), and unmodified BSA. RESULTS: Renal proximal tubular cells handle MGO-BSA and native BSA in markedly disparate ways, including differences in: (1) kinetics of binding, uptake, and intracellular accumulation, (2) processing and fragmentation, and (3) patterns of electrical conductance paralleling temporal changes in binding, uptake and processing. CONCLUSION: These differences support the idea that abnormal protein processing by the renal tubule can be caused by abnormal proteins, thereby forging a conceptual link between the pathogenic role of AGEs and early changes in tubular function that can lead to hypertrophy and nephropathy in diabetes. (c) 2007 S. Karger AG, Basel.
AIM: The goal of this work is to understand the cellular effects of advanced glycation end product (AGE)-modified protein on renal proximal tubule cells. BACKGROUND: A major function of the proximal tubule is to reabsorb and process filtered proteins. Diabetes is characterized by increased quantities of tissue and circulating proteins modified by AGEs. Therefore in diabetes, plasma proteins filtered at the glomerulus and presented to the renal proximal tubule are likely to be highly modified by AGEs. METHODS: The model system was electrically resistant polarized renal proximal tubular epithelial cells in monolayer culture. The model proteins comprise a well-characterized AGE, methylglyoxal-modified bovine serum albumin (MGO-BSA), and unmodified BSA. RESULTS: Renal proximal tubular cells handle MGO-BSA and native BSA in markedly disparate ways, including differences in: (1) kinetics of binding, uptake, and intracellular accumulation, (2) processing and fragmentation, and (3) patterns of electrical conductance paralleling temporal changes in binding, uptake and processing. CONCLUSION: These differences support the idea that abnormal protein processing by the renal tubule can be caused by abnormal proteins, thereby forging a conceptual link between the pathogenic role of AGEs and early changes in tubular function that can lead to hypertrophy and nephropathy in diabetes. (c) 2007 S. Karger AG, Basel.
Authors: Tomoaki Uchiki; Karen A Weikel; Wangwang Jiao; Fu Shang; Andrea Caceres; Dorota Pawlak; James T Handa; Michael Brownlee; Ram Nagaraj; Allen Taylor Journal: Aging Cell Date: 2011-11-15 Impact factor: 9.304
Authors: Edwin J Vazquez; Jessica M Berthiaume; Vasudeva Kamath; Olisaemeka Achike; Elizabeth Buchanan; Monica M Montano; Margaret P Chandler; Masaru Miyagi; Mariana G Rosca Journal: Cardiovasc Res Date: 2015-06-22 Impact factor: 10.787
Authors: Christine P Limonte; Erkka Valo; Viktor Drel; Loki Natarajan; Manjula Darshi; Carol Forsblom; Clark M Henderson; Andrew N Hoofnagle; Wenjun Ju; Matthias Kretzler; Daniel Montemayor; Viji Nair; Robert G Nelson; John F O'Toole; Robert D Toto; Sylvia E Rosas; John Ruzinski; Niina Sandholm; Insa M Schmidt; Tomas Vaisar; Sushrut S Waikar; Jing Zhang; Peter Rossing; Tarunveer S Ahluwalia; Per-Henrik Groop; Subramaniam Pennathur; Janet K Snell-Bergeon; Tina Costacou; Trevor J Orchard; Kumar Sharma; Ian H de Boer Journal: Diabetes Care Date: 2022-06-02 Impact factor: 17.152