Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product
| Autor: | Toshio Miyata, Takehiko Wada, C. Van Ypersele De Strihou, Kiyoshi Kurokawa, Yasuhiko Ueda, Michel Jadoul, Y Yamada, Yuko Izuhara, Akira Saito |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Glycosylation medicine.medical_treatment Carboxylic Acids Ultrafiltration Deoxyglucose Arginine Guanidines chemistry.chemical_compound symbols.namesake Renal Dialysis Glycation Internal medicine Thiadiazoles medicine Humans Pentosidine Aged Uremia Aldehydes Lysine Esters General Medicine Ketones Middle Aged medicine.disease Human serum albumin Ascorbic acid Maillard Reaction Phenylhydrazines Molecular Weight Maillard reaction Endocrinology chemistry Nephrology Depression Chemical symbols Thiazolidines Advanced glycation end-product Hemodialysis medicine.drug |
| Zdroj: | Journal of the American Society of Nephrology. 9:2349-2356 |
| ISSN: | 1046-6673 |
| DOI: | 10.1681/asn.v9122349 |
| Popis: | Advanced glycation end product (AGE) formation is related to hyperglycemia in diabetes but not in uremia, because plasma AGE levels do not differ between diabetic and nondiabetic hemodialysis patients. The mechanism of this phenomenon remains elusive. Previously, it was suggested that elevation of AGE levels in uremia might result from the accumulation of unknown AGE precursors. The present study evaluates the in vitro generation of pentosidine, a well identified AGE structure. Plasma samples from healthy subjects and nondiabetic hemodialysis patients were incubated under air for several weeks. Pentosidine levels were determined al:intervals by HPLC assay. Pentosidine rose to a much larger extent in uremic than in control plasma. Pentosidine yield, i.e., the change in pentosidine level between 0 and 4 wk divided by 28 d, averaged 0.172 nmol/ml per d in uremic versus 0.072 nmol/ml per d in control plasma (P < 0.01). The difference in pentosidine yield between uremic and control plasma was maintained in samples ultrafiltrated through a filter with a 5000-Da cutoff value and fortified with human serum albumin (0.099 versus 0.064 nmol/ml per d; P < 0.05). Pentosidine yield was higher in pre- than in postdialysis plasma samples (0.223 versus 0.153 nmol/ml per d; P < 0.05). These results suggest that a large fraction of the pentosidine precursors accumulated in uremic plasma have a lower than 5000 Da molecular weight. Addition of aminoguanidine and OPB-9195, which inhibit the Maillard reaction, lowered pentosidine yield in both uremic and control plasma. When ultrafiltrated plasma was exposed to 2,4-dinitrophenylhydrazine, the yield of hydrazones, formed by interaction with carbonyl groups, was markedly higher in uremic than in control plasma. These observations strongly suggest that the pentosidine precursors accumulated in uremic plasma are carbonyl compounds. These precursors are unrelated to glucose or ascorbic acid, whose concentration is either normal or lowered in uremic plasma. They are also unrelated to 3-deoxyglucosone, a glucose-derived dicarbonyl compound whose level is raised in uremic plasma: Its addition to normal plasma fails to increase pentosidine yield. This study reports an elevated level of reactive carbonyl compounds ("carbonyl stress") in uremic plasma. Most have a lower than 5000 Da molecular weight and are thus partly removed by hemodialysis. Their effect on pentosidine generation can be inhibited by aminoguanidine or OPB-9195. Carbonyl stress might contribute to AGE modification of proteins and thus to clinically relevant complications of uremia. |
| Databáze: | OpenAIRE |
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