Disease relevance of Pentosidine

• NEWLY OBSERVED FINDINGS: Significant elevation of pentosidine (P = 0.025) was found in subjects with microalbuminuria or gross proteinuria (73.03 +/- 9.47 vs 76.46 +/- 6.37 pmol/mg col) when compared with normal (56.96 +/- 3.26 pmol/mg col) [1].
• FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively) [2].
• OBJECTIVES: To evaluate the role of AGEs in the development of diabetic nephropathy and retinopathy, we studied pentosidine levels and the clinical characteristics of 48 subjects with insulin-dependent diabetes mellitus [1].
• Identification of pentosidine as a native structure for advanced glycation end products in beta-2-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis [3].
• Diabetes, and especially uremia, greatly catalyzes pentosidine formation [4].

Psychiatry related information on Pentosidine

• Furthermore, involvement of the Maillard reaction with Alzheimer's disease has also been suggested, as advanced glycation end products, such as pyrraline and pentosidine, were demonstrated to localize in lesions of the disease [5].
• Pentosidine and N(epsilon)-(carboxymethyl)-lysine in Alzheimer's disease and vascular dementia [6].
• It is not known whether pentosidine itself is directly associated with erectile dysfunction, but its formation is usually accompanied by extensive tissue modification [7].

High impact information on Pentosidine

• Since oxidation is linked closely to the formation of pentosidine and CML, we also immunostained malondialdehyde (MDA), a lipid peroxidation product whose formation is accelerated by oxidative stress, assuming that local oxidative stress may serve as a mechanism of pentosidine and CML accumulation [8].
• These findings show that AGE localization in DN varies according to AGE structure, and suggest that the colocalization of markers of glycoxidation (pentosidine and CML) with a marker of lipid peroxidation reflects a local oxidative stress in association with the pathogenesis of diabetic glomerular lesions [8].
• Although the distribution of pyrraline was topographically identical to type III collagen, distribution of pentosidine and CML was not specific for collagen type, suggesting that difference in matrix protein composition per se could not explain heterogeneous AGE localization [8].
• The HD treatment decreased free and < 10,000 mol wt bound pentosidine [9].
• METHODS: Liver pyridinoline and pentosidine were analyzed by high-performance liquid chromatography, and urinary pyridinoline was analyzed by immunoassay [10].

Chemical compound and disease context of Pentosidine

• Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation [11].
• Although the data suggested a role for ascorbate in pentosidine formation in senile cataractous lenses, elevated pentosidine levels in diabetic cataracts suggested that glucosylation may be involved directly in pentosidine biosynthesis [12].
• The requirement of oxygen for pentosidine formation suggests that oxidative stress associated with glutathione depletion and ascorbate oxidation are plausible mechanisms for rapid pentosidine formation upon onset of galactosemia [12].
• It suggests the simultaneous accumulation, during renal failure, of either unknown pentosidine precursor(s) or catalyst(s) of glycoxidation, independent of glucose [13].
• In diabetic patients, including patients with renal failure, plasma pentosidine levels, assessed by HPLC assay, were correlated with serum creatinine (P < 0.0001) [14].

Biological context of Pentosidine

• Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with control patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress [15].
• Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy [1].
• No true pentosidine was formed during acid hydrolysis of ribated protein, suggesting that Amadori products do not generate artifactual pentosidine during hydrolysis [16].
• Lysine residues within actuator and phosphorylation domains were cross-linked to arginine residues within the nucleotide binding domain via pentosidine AGEs [17].
• Currently, the mechanism of accumulation and kinetics of pentosidine formation in hemodialysis patients remain unknown [13].

Anatomical context of Pentosidine

• These data suggest that fluorescence in skin and tendon might be in part due to advanced glycosylation and pentosidine formation because these were not decreased by ARI [18].
• In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidine [19].
• Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects [16].
• Thus, whereas protein glycation and advanced glycation in the extracellular matrix and in the lens are generally related to the level of glycemic control, there is evidence for a tissue-specific glycemic threshold for pentosidine formation, i.e., glycoxidation, in the lens [20].
• Furthermore, pentosidine in plasma proteins may act as a signal for advanced glycosylation end product-mediated receptor uptake by macrophages and other cells and contribute to accelerated atherosclerosis in diabetes and uremia [16].

Associations of Pentosidine with other chemical compounds

• FL, CML, pentosidine, and fluorescence were also elevated in patients with early nephropathy (P < 0.05, P < 0.001, P < 0.01, P < 0.01, respectively) [2].
• Levels correlate with degree of lens crystallin pigmentation and fluorescence and are increased in diabetes, in contrast to N(epsilon)-(carboxymethyl)lysine and pentosidine [21].
• The discovery that pentosidine can form not only from pentoses but also from hexoses and ascorbate raises major new questions concerning biochemical pathways of the Maillard reaction in vivo [22].
• The yield of pentosidine from N alpha-t-Boc-lysine, N alpha-t-Boc-arginine, and D-ribose was highest at pH 9.0 and 65 degrees C, but was unaffected by reactant ratios at alkaline pH suggesting an important role for base catalysis [22].
• ROD patients had the highest mean level of pentosidine (407 mumoles/mole of hydroxyproline), and RA patients had a higher mean level than age-matched OA patients (214 versus 103 mumoles/mole of hydroxyproline) [23].

Gene context of Pentosidine

• In the latter, VEGF colocalized with the advanced glycation end product pentosidine deposits [24].
• RESULTS: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group [25].
• Markers for oxidative stress were advanced oxidation products (AOPP), myeloperoxidase (MPO)-activity, pentosidine and carboxymethyl lysine (CML) [26].
• Among markers of inflammation and matrix destruction, pentosidine levels in plasma from RA patients were correlated with the levels of C-reactive protein (CRP), erythrocyte sedimentation rate, white blood cell count, and platelet count [27].
• Multiple stepwise regression analysis reveals an independent influence of CRP on plasma pentosidine levels [27].

Analytical, diagnostic and therapeutic context of Pentosidine

• Fractionation by gel filtration of serum from patients on PD and HD revealed that > 95% of the pentosidine was linked to proteins > 10,000 mol wt; < 1% to proteins < 10,000 mol wt; and < 1%, free [9].
• Determination by both HPLC assay and competitive ELISA demonstrated a significant amount of pentosidine in amyloid-fibril beta-2m from long-term hemodialysis patients with DRA, and the acidic isoform of beta-2m in the serum and urine of hemodialysis patients [3].
• A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and beta-2m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients with DRA [3].
• By contrast, the inhibition of renal pentosidine formation assessed both by immunohistochemistry and HPLC suggests a critical role of advanced glycation end product (AGE) formation together with hypertension in the genesis of diabetic nephropathy [28].
• ELISA of pentosidine, an advanced glycation end product, in biological specimens [29].

References