Abstract
Pentosidine is an advanced glycation end product, formed by oxidation and glycation that accumulates markedly during end-stage renal failure. Measurement of the pentosidine level in physiological samples is applied as a sensitive marker for the early diagnosis of renal failure. In the quantitative measurements of pentosidine reported to date, a rapid enzyme-linked immunosorbent assay (ELISA) has been widely used to estimate the plasma/serum pentosidine levels in a number of clinical samples, because high performance liquid chromatography (HPLC) methods require multiple preparation steps before the analysis. However, the currently used clinical analysis of the plasma/serum pentosidine level by ELISA requires incubation of the plasma/serum at 100°C for 15 min to inactivate the protease, which is required before the anti-pentosidine antibody can bind to the pentosidine. In the present study, we examined whether pentosidine could be generated artificially through the heating of serum. The pentosidine content, measured by HPLC, in the serum increased by heating in a temperature- and time-dependent manner. The pentosidine content was increased 1.1- to 4.2-fold by the heating process compared to unheated samples, and the increased rate was not identical for each sample. After removing low-molecular weight (<10,000) serum components, the heat-induced pentosidine formation was decreased. Furthermore, the increase in pentosidine formation was significantly inhibited by acidic conditions more than by the addition of diethylene triamine pentaacetic acid, a metal chelator. This indicates that the level of serum pentosidine will be measured more accurately by ELISA if hydrochloric acid is added during the heating process.
References
Ahmed MU, Thorpe SR, Baynes JW (1986) Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J Biol Chem 261:4889–4894
Ahmed MU, Frye EB, Degenhardt TP, Thorpe SR, Baynes JW (1997) N ε-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins. Biochem J 324:565–570
Brownlee M, Vlassara H, Kooney A, Ulrich P, Cerami A (1986) Aminoguanidine prevents diabetes-induced arterial wall protien cross-linking. Science 232:1629–1632
Grandhee SK, Monnier VM (1991) Mechanism of formation of the Maillard protein cross-link pentosidine. Glucose, fructose, and ascorbate as pentosidine precursors. J Biol Chem 266:11649–11653
Hayashi MC, Nagai R, Miyazaki K, Hayase F, Araki T, Ono T, Horiuchi S (2002) Conversion of Amadori products of the Maillard reaction to N ε-(carboxymethyl)lysine by short-term heating: possible detection of artifacts by immunohistochemistry. Lab Invest 82:795–808
Iijima K, Murata M, Takahara H, Irie S, Fujimoto D (2000) Identification of N(omega)-carboxymethylarginine as a novel acid-labile advanced glycation end product in collagen. Biochem J 347:23–27
Izuhara Y, Miyata T, Ueda Y, Suzuki D, Asahi K, Inagi R, Sakai H, Kurokawa K (1999) A sensitive and specific ELISA for plasma pentosidine. Nephrol Dial Transplant 14:576–580
Konishi Y, Hayase F, Kato H (1994) Novel imidazolones compound formed by the advanced Maillard reaction of 3-deoxyglucosone and arginine residues in proteins. Biosci Biotechnol Biochem 58:1953–1955
Maillard LC (1912) Action des acides amines sur les sucres: formation des melanoidines par voie methodique. C R Acad Sci 154:66–68 (Paris)
Miyata T, Ueda Y, Shinzato T, Iida Y, Tanaka S, Kurokawa K (1996) Accumulation of albumin-linked and free-form pentosidine in the circulation of uremic patients with end-stage renal failure: renal implications in the pathophysiology of pentosidine. J Am Soc Nephrol 7:1198–1206
Miyata T, Ueda Y, Yamada Y, Izuhara Y, Wada T, Jadol M, Saito A, Kurokawa K, Strihou CY (1998) Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: carbonyl stress in uremia. J Am Soc Nephrol 9:2349–2356
Miyata T, Horie K, Ueda Y, Fujita Y, Izuhara Y, Hirano H, Uchida K, Saito A, de Strihou C, Kurokawa K (2000) Advanced glycation and lipidoxidation of the peritoneal membrane: respective roles of serum and peritoneal fluid reactive carbonyl compounds. Kidney Int 58:425–435
Motomura K, Fujiwara Y, Kiyota N, Tsurushima K, Takeya M, Nohara T, Nagai R, Ikeda T (2009) Astragalosides isolated from the root of astragalus radix inhibit the formation of advanced glycation end products. Agric Food Chem 57:7666–7672
Nagai R, Ikeda K, Higashi T, Sano H, Jinnouchi Y, Araki T, Horiuchi S (1997) Hydroxyl radical mediates N ε-(carboxymethyl) lysine formation from Amadori product. Biochem Biophys Res Commun 234:167–172
Portero-Otin M, Nagaraj RH, Monnier VM (1995) Chromatographic evidence for pyrraline formation during protein glycation in vitro and in vivo. Biochim Biophys Acta 1247:74–80
Sajithlal GB, Chithra P, Chandrakasan G (1998) The role of metal-catalyzed oxidation in the formation of advanced glycation end products: an in vitro study on collagen. Free Radic Biol Med 25:265–269
Sanaka T, Niwayama J, Shiomi T, Kimura T, Nishimura H, Nakamura K (1999) Development of competitive ELISA methods for plasma pentosidine concentration and the analysis of the patients with chronic renal failure. Jin to touseki 47:867–872 (Japanese)
Sanaka T, Funaki T, Tanaka T, Hoshi S, Niwayama J, Taitoh T, Nishimura H, Higuchi C (2002) Plasma pentosidine levels measured by a newly developed method using ELISA in patients with chronic renal failure. Nephron 91:64–73
Sell DR, Monnier VM (1989) Structure elucidation of a senescence cross-link from human extracellular matrix. J Biol Chem 264:21597–21602
Taneda S, Monnier VM (1994) ELISA of pentosidine, an advanced glycation end product, in biological specimens. Clin Chem 40:1766–1773
Tsukahara H, Sekine K, Uchiyama M, Kawakami H, Hata I, Todoroki Y, Hiraoka M, Kaji M, Yorifuji T, Momoi T, Yoshihara K, Beppu M, Mayumi M (2003) Formation of advanced glycosylation end products and oxidative stress in young patients with type 1 diabetes. Pediatr Res 54:419–424
Weiss MF, Rodby RA, Justice AC, Hricik DE (1998) Free pentosidine and neopterin as markers of progression rate in diabetic nephropathy. Kidney Int 54:193–202
Yoshihara K, Nakamura K, Kanai M, Nagayama Y, Takahashi S, Saito N, Nagata M (1998) Determination of urinary and serum pentosidine and its application to elder patients. Biol Pharm Bull 21:1005–1008
Acknowledgments
We are grateful to Mime Nagai and Satoko Shimasaki for their collaborative endeavors. This work was supported in part by a Grant-in-Aid for Scientific Research (No. 18790619 to Ryoji Nagai) from the Ministry of Education, Science, Sports and Cultures of Japan.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Nakano, M., Kubota, M., Owada, S. et al. The pentosidine concentration in human blood specimens is affected by heating. Amino Acids 44, 1451–1456 (2013). https://doi.org/10.1007/s00726-011-1180-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-011-1180-z