TY - JOUR
T1 - Renal catabolism of advanced glycation end products
T2 - The fate of pentosidine
AU - Miyata, Toshio
AU - Ueda, Yasuhiko
AU - Horie, Katsunori
AU - Nangaku, Masaomi
AU - Tanaka, Shuichi
AU - Van Ypersele De Strihou, Charles
AU - Kurokawa, Kiyoshi
N1 - Funding Information:
This study was supported by grants from Research for the Future Program of the Japan Society for the Promotion of Science (96L00303).
PY - 1998
Y1 - 1998
N2 - Advanced glycation end products (AGEs) generated through the Maillard reaction significantly alter protein characteristics. Their accumulation has been incriminated in tissue injury associated with aging, diabetes, and renal failure. However, little is known about their clearance from the body. The present study delineates the catabolic pathway of a well-defined AGE product, pentosidine. Synthesized pentosidine given intravenously in rats with normal renal function was rapidly eliminated from the circulation through glomerular filtration, but was undetectable in the urine by chemical analysis. Immunohistochemistry with anti-pentosidine antibody disclosed that pentosidine accumulated transiently in the proximal renal tubule one hour after its administration, but had disappeared from the kidney at 24 hours. After an intravenous load of radiolabeled pentosidine, radioactivity peaked in the kidney at one hour and subsequently decreased, whereas it rose progressively in the urine. Over 80% of the radioactivity was recovered in the 72-hour collected urine. However, only 20% of urine radioactivity was associated with intact pentosidine chemically or immunochemically. In gentamicin-treated rats with tubular dysfunction, up to 30% of the pentosidine load was recovered as intact pentosidine in the urine. The present study suggests that free pentosidine (and possibly other AGEs) is filtered by renal glomeruli, reabsorbed in the proximal tubule where it is degraded or modified, and eventually excreted in the urine. Kidney thus plays a key role in pentosidine disposal.
AB - Advanced glycation end products (AGEs) generated through the Maillard reaction significantly alter protein characteristics. Their accumulation has been incriminated in tissue injury associated with aging, diabetes, and renal failure. However, little is known about their clearance from the body. The present study delineates the catabolic pathway of a well-defined AGE product, pentosidine. Synthesized pentosidine given intravenously in rats with normal renal function was rapidly eliminated from the circulation through glomerular filtration, but was undetectable in the urine by chemical analysis. Immunohistochemistry with anti-pentosidine antibody disclosed that pentosidine accumulated transiently in the proximal renal tubule one hour after its administration, but had disappeared from the kidney at 24 hours. After an intravenous load of radiolabeled pentosidine, radioactivity peaked in the kidney at one hour and subsequently decreased, whereas it rose progressively in the urine. Over 80% of the radioactivity was recovered in the 72-hour collected urine. However, only 20% of urine radioactivity was associated with intact pentosidine chemically or immunochemically. In gentamicin-treated rats with tubular dysfunction, up to 30% of the pentosidine load was recovered as intact pentosidine in the urine. The present study suggests that free pentosidine (and possibly other AGEs) is filtered by renal glomeruli, reabsorbed in the proximal tubule where it is degraded or modified, and eventually excreted in the urine. Kidney thus plays a key role in pentosidine disposal.
KW - Advanced glycation end products
KW - Pentosidine
KW - Protein
KW - Tissue injury
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U2 - 10.1046/j.1523-1755.1998.00756.x
DO - 10.1046/j.1523-1755.1998.00756.x
M3 - Article
C2 - 9461101
AN - SCOPUS:0031930853
VL - 53
SP - 416
EP - 422
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 2
ER -