Disease relevance of C06195

• These results, taken together with a recent demonstration of increased serum 3-DG levels in diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term diabetic complications such as nephropathy and atherosclerosis [1].
• Four intravenous doses of piroximone, an imidazolone derivative, were administered to 12 patients with congestive heart failure to produce a four-point dose-response curve [2].
• Amyloid beta 2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis [3].
• Some investigators measured individual AGE compounds, e.g. pentosidine, carboxymethyllysine, pyrraline or imidazolone, but a systematic assessment of known compounds using specific HPLC methods in diabetic and non-diabetic end-stage renal disease (ESRD) patients during treatment has not been performed [4].
• In contrast, no immunoreactivity to CML, pyrraline, pentosidine, imidazolone or CEL was detected in corneas with bullous keratopathy, or in corneas without any corneal diseases [5].

High impact information on C06195

• The imidazolone levels in the erythrocytes of diabetic patients were found to be significantly increased as compared with those of healthy subjects [1].
• Then we studied the localization of imidazolone in the kidneys and aortas obtained from diabetic patients by immunohistochemistry using the antibody [1].
• This study first demonstrates the localization of imidazolone in the characteristic lesions of diabetic nephropathy and atherosclerosis [1].
• We determined the erythrocyte levels of imidazolone in diabetic patients using ELISA with the monoclonal anti-imidazolone antibody [1].
• Specific imidazolone immunoreactivity was detected in nodular lesions and expanded mesangial matrix of glomeruli, and renal arteries in an advanced stage of diabetic nephropathy, as well as in atherosclerotic lesions of aortas [1].

Chemical compound and disease context of C06195

• Using an antibody specific to this 3-DG-derived AGE, we demonstrated the presence of imidazolone-modified proteins in vivo in the urine and dialysate of patients with chronic renal failure, in the synovial fluid of patients with rheumatoid arthritis, as well as in vitro in human serum and human serum albumin incubated with glucose [6].

Biological context of C06195

• Serum samples were assayed for circulating advanced glycosylation end products (AGE), N(epsilon)-(carboxymethyl)lysine (CML), and imidazolone [7].
• Immunochemistry demonstrated that the imidazolone content in the kidneys of streptozotocin-induced diabetic rats was significantly higher than in the control rats [8].
• The objective and timing of drug disposition studies, appendix I. Species differences in the tissue distribution of metazimid, an imidazolone derivative [9].
• A key feature of the synthesis is a putative biomimetic, intramolecular cyclization of alpha-functionalized imidazolone 5, which affords the tricyclic pyrroloazepinone framework comprising 6 [10].
• Recently, imidazolone (Iz), guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) have been demonstrated as oxidative lesion products of guanine and 8-oxoG, which could be responsible for G-C to C-G transversions by forming specific base pair formations [11].

Anatomical context of C06195

• Immunohistochemical detection of imidazolone, a novel advanced glycation end product, in kidneys and aortas of diabetic patients [1].
• Western blotting using the antibody demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone [3].
• In the familial ALS cases, intense immunoreactivities for pyrraline and CML were confined to the characteristic Lewy body-like hyaline inclusions, and imidazolone immunoreactivity was located in the cytoplasm of the residual motor neurons [12].
• Localization of imidazolone in the peritoneum of capd patients: a factor for a loss of ultrafiltration [13].
• Imidazolone levels in blood serum decrease significantly after switching from single- to double-chamber PDFs [14].

Associations of C06195 with other chemical compounds

• Irreversible modification of BSA occurred mainly on arginine residues to form imidazolone [15].
• RESULTS: The erythrocyte levels of sorbitol, 3-DG, imidazolone, and CML were significantly elevated in diabetic HD patients as compared with healthy subjects [16].
• This study aimed to investigate whether elevated serum levels of the AGEs pentosidine, N(epsilon)-carboxymethyllysine (CML) and imidazolone; tHcy, cystathionine, methylmalonic acid (MMA), and 2-methylcitric acid (2-MCA), as well as C-reactive protein (CRP), are related to a higher risk for cardiovascular events [17].
• Trapping by O2(-)(*) leads to the oxaluric acid (pH <or= 7) and imidazolone (pH >or= 8.6) pathways (R' ', R' ' = H or 2,3,5-tri-O-Ac-ribofuranosyl) [18].
• Western blot analysis was used to detect imidazolone, pentosidine, and CML in the aqueous [19].

Gene context of C06195

• Serum CML and imidazolone levels fell significantly in balance-treated patients [7].
• Then we determined the localization of imidazolone in the amyloid tissues by immunohistochemistry using the antibody [3].
• 3-DG accumulating in uremic serum may be involved in the modification of beta 2m with imidazolone [3].
• Affinity purification of AGE-modified proteins from IC and immunoblotting with antibodies against Ig gamma and mu heavy chains, kappa and lambda light chains, and AGE Nepsilon(carboxymethyl)lysine and imidazolone yielded similar results: anti-AGE+ RA patients had elevated levels relative to those without the autoantibody [20].
• METHODS: Immunohistochemical localisation of N(epsilon)-(carboxymethyl)-l-lysine (CML), N(epsilon)-(carboxyethyl)-l-lysine (CEL), pyrraline, pentosidine and imidazolone was examined in three corneas with CDK, six corneas with bullous keratopathy and three corneas without any corneal diseases [5].

Analytical, diagnostic and therapeutic context of C06195

• The formation of late glycation products was assessed by fluorescence spectroscopy and Western blotting that used a specific antibody for imidazolone, a late glycation product [21].
• To determine if 3-DG is involved in the formation of intracellular AGEs, we measured the erythrocyte levels of 3-DG and AGEs such as imidazolone and N epsilon-carboxymethyllysine (CML) in hemodialysis (HD) patients with diabetes [16].
• Liquid chromatography/mass spectrometry demonstrated that the formation of imidazolone A by incubating 3-DG with arginine is very rapid, reaching a maximum concentration within 24 h, but the formation of imidazolone B is very slow and low in quantity even after 2 weeks [8].
• In conclusion, the accumulation of imidazolone was noted in peritoneal tissues of CAPD patients, which preceded a decrease in UF capacity [13].

References