Das Apoptose-Markerenzym Poly-(ADP-Ribose-)Polymerase (PARP) beim systemischen Lupus erythematodes

Böhm, Ingrid

doi:10.1007/s00393-006-0045-4

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…72 Since our study shows that PARP-1 is a critical regulator of IL-10 gene expression in the context of SLE, it will be of significance to investigate the expression and activity of PARP-1 in SLE patients' macrophages following phagocytosis of apoptotic cells, as a way to understand the genetic basis and pathophysiology of SLE.…”

Section: Parp-1 Regulates Il-10 Snp-mediated Transcriptionmentioning

confidence: 94%

“…Serum samples from SLE patients and other autoimmune diseases display anti-PAR and anti-PARP autoantibodies. 72 In particular, autoantibodies to the catalytic fragment of PARP-1 were found in the sera of nearly 50% patients with SLE whereas they were not present in the sera of patients with rheumatoid arthritis, systemic sclerosis or healthy donors. 73,74 It is noted that in the standard 'supershift' experiment in Figure 4d, all three antibodies caused a neutralizing effect rather than a 'supershifting' one.…”

Section: Parp-1 Regulates Il-10 Snp-mediated Transcription Ey Chung Ementioning

confidence: 97%

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Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

et al. 2007

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Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease characterized by the dysregulation of T and B cells that leads to hyperactivity of B cells and production of autoantibodies, and involves both environmental and genetic factors. Interleukin-10 (IL-10) is a candidate susceptibility gene in SLE. In particular, three IL-10 promoter singlenucleotide polymorphisms (SNPs; À1082A/G, À819T/C and À592A/C) are strongly associated with the pathogenesis of SLE. We found that the homozygous GCC haplotype linked to greater SLE severity confers higher IL-10 gene transcriptional activity than the ATA haplotype in macrophages that encounter apoptotic cells, because of the differential DNA binding to the À592 SNP by a nuclear protein uniquely induced by apoptotic cells. We identified this protein as poly(ADP-ribose) polymerase-1, confirmed its physiological role and characterized its molecular properties in modulating IL-10 production during phagocytosis of apoptotic cells. This study unveils a novel direct link between DNA damage repair/apoptosis pathways and IL-10-mediated immune regulation.

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Section: Parp-1 Regulates Il-10 Snp-mediated Transcriptionmentioning

confidence: 94%

Section: Parp-1 Regulates Il-10 Snp-mediated Transcription Ey Chung Ementioning

confidence: 97%

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

et al. 2007

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“…24 During apoptosis, PARP is cleaved by caspase 3 with an ensuing reduction in PARP enzyme activity, which thus prevents apoptotic cells from repairing their own DNA. 25 PARP activity in Mf exposed to nanosilver (50 µM), nanogold (50 µM), or staurosporine (0.5 µM) was then studied. Both AgNPs and staurosporine induced nearly 70% attenuation in PARP enzymatic activity, whereas only 25% loss in activity was observed in the presence of AuNPs (Table 2), thus consistent with the significant microfilaricidal effect of nanoscale silver.…”

Section: Resultsmentioning

confidence: 99%

Novel microfilaricidal activity of nanosilver

Singh¹,

Goswami²,

Sharma³

et al. 2012

IJN

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Purpose:The currently available drug repertoire against lymphatic filariasis, a major health hazard in the developing world, is inadequate and is fraught with serious limitations. Thus, the development of an effective antifilarial strategy has become a global research thrust mandated by the World Health Organization. Nanoparticles of silver endowed with antibacterial potency are known to induce apoptosis in eukaryotic cells. The present study was designed to investigate the possible microfilaricidal efficacy of silver nanoparticles and to establish the validity of apoptotic rationale in antifilarial drug designing. Methods: This report analyzed the effect of nanoparticles of silver as well as gold (size range: 10-15 nm) on the microfilariae of Brugia malayi obtained from the lavage of peritoneal cavities of infected jirds (Meriones unguiculatus). The study included a microfilarial motility assay, a trypan blue exclusion test, a poly(adenosine diphosphate-ribose) polymerase activity study, ethidium bromide/acridine orange differential staining, and transmission, as well as scanning electron microscopic evaluation of ultrastructural changes in microfilariae. Results: The study demonstrates that nanoparticles of silver, but not of gold, elicited significant loss in microfilarial motility. Differential staining of parasites with ethidium bromide and acridine orange, poly(adenosine diphosphate-ribose) polymerase activity in microfilarial lysate, and electron microscopic findings underscored apoptotic death of parasites attributable to nanosilver. In a trypan blue exclusion test, the 50% lethal dose of nanosilver was measured to be 101.2 µM, which was higher than the recorded complete inhibitory concentration value (50.6 µM), thus supporting nanosilver as a potential drug candidate against lymphatic filariasis. Conclusion:The present report provides the first ever conclusive proof in support of apoptosis as a novel stratagem in antifilarial drug designing and nanoscale silver as a valid lead in research on antifilarial therapeutics. The main embargo about the current drug diethylcarbamazine citrate is its empirical use without rationale. Effective microfilaricidal activity of nanosilver at relatively low concentrations as reported in this study, with evidence of the induction of apoptosis in microfilariae, projects nanosilver as a potential drug adjuvant against lymphatic filariasis. The much higher 50% lethal dose value of nanosilver compared to the complete inhibitory concentration value reported in this study argues in favor of a safe therapeutic window of this agent in its antifilarial efficacy.

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“…PARP cleavage products are mainly found in association with either antinuclear or anti-dsDNA antibodies. Serum samples from SLE patients and other autoimmune diseases display anti-PAR and anti-PARP autoantibodies (Böhm 2006). In particular, autoantibodies to the catalytic fragment of PARP-1 were found in the sera of nearly 50% patients with SLE while they were not present in the sera of patients with rheumatoid arthritis, systemic sclerosis, or healthy donors (Lim and others 2002;Jeoung and others 2004).…”

Section: Il-10 Gene Expression During Phagocytosis Of Apoptotic Cellsmentioning

confidence: 99%

Regulation of Interleukin-10 Gene Expression in Macrophages Engulfing Apoptotic Cells

Zhang

Kim

Yamamoto

et al. 2010

Journal of Interferon & Cytokine Research

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Das Apoptose-Markerenzym Poly-(ADP-Ribose-)Polymerase (PARP) beim systemischen Lupus erythematodes

Cited by 8 publications

References 37 publications

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

Novel microfilaricidal activity of nanosilver

Regulation of Interleukin-10 Gene Expression in Macrophages Engulfing Apoptotic Cells

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