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The article examines whether low molecular weight oligonucleosomes can be found in the kidneys of autoimmune mice. The authors also investigate whether the presence of glomerular membrane-associated TUNEL-positive electron-dense structure hints at the existence of low molecular weight oligonucleosomes. They report that results have shown that TUNEL-positive chromatin particles are deposited in nephritic mice's glomeruli, due to chromatin clearance and reduced fragmentation.

Advanced glycation end products (AGEs) are known to be associated with a number of pathological conditions, such as diabetes mellitus, Alzheimer’s disease, uremia, as well as with normal aging. This study was undertaken to investigate whether Nϵ-(carboxymethyl)lysine (CML), a major structure among numerous AGEs, engenders hepatic AGE clearance. For this purpose uptake of BSA substituted with heterogeneous AGEs or with CML only was monitored in vivo and in cultured hepatic scavenger cells. Here, we show that following intravenous administration of 125I-AGE–BSA and 125I-CML–BSA, blood radioactivity was reduced by 50% after 50 s and >100 min, respectively. Recoveries from the circulation at 6 min after injection were: 5% for AGE–BSA, 95% for CML–BSA. More than 80% of the injected AGE–BSA was recovered from the liver. AGE–BSA, but not CML–BSA, was avidly endocytosed by cultured liver scavenger cells. Our results suggest that CML does not engender AGE–BSA clearance. Macromolecules substituted with CML only may escape elimination and cause pathological effects. [Copyright &y& Elsevier]

Objective: Antinucleosome autoantibodies are pathogenic factors in lupus nephritis. Defects in apoptotic pathways may result in increased levels of apoptotic nucleosomes. The objectives of this study were 1) to determine whether low molecular weight oligonucleosomes are present in the kidneys of autoimmune (NZB x NZW)F(1) mice, 2) to analyze whether the presence of glomerular membrane-associated TUNEL-positive electron-dense structures reflect the existence of low molecular weight oligonucleosomes, and 3) to determine an eventual temporal relationship between glomerular electron-dense structures, oligonucleosomes, and proteinuria in these mice., Methods: DNA was isolated from mouse 111s34 hybridoma cells and from the kidneys of normal BALB/c mice in which apoptosis was induced by camptothecin and from the kidneys of (NZB x NZW)F(1) mice at ages 4 weeks, 8 weeks, 20 weeks, and > or = 26 weeks (nephritic mice). The DNA fragmentation pattern was determined with an Agilent bioanalyzer. An electron microscopy-based TUNEL assay was performed to detect apoptotic chromatin in glomerular membranes, and immunoelectron microscopy was used to determine antibody binding. Transcription levels for nucleases associated with apoptosis and necrosis were determined by real-time polymerase chain reaction., Results: DNA from camptothecin-treated cell lines and BALB/c mouse kidneys, but not that from untreated (NZB x NZW)F(1) mouse kidneys, demonstrated DNA cleavage consistent with apoptotic fragmentation. DNA from (NZB x NZW)F(1) mice was devoid of apoptotic fragmentation, irrespective of the age of the mice, whereas TUNEL-positive chromatin particles were detected in glomerular membranes in nephritic mice. Renal DNase I transcription was reduced in nephritic mice. Nucleosomal DNA fragmentation in response to camptothecin exposure was highly reduced in (NZB x NZW)F(1) mouse kidneys compared with that in their normal counterparts., Conclusion: The results of this study demonstrate that TUNEL-positive chromatin particles are deposited in the glomeruli of nephritic (NZB x NZW)F(1) mice, due to reduced fragmentation and clearance of chromatin.