8‐Hydroxydeoxyguanosine

Lunec, Joseph; Herbert, Karl E.; Blount, Susan; Griffiths, Helen R.; Emery, Paul

doi:10.1016/0014-5793(94)00583-4

Cited by 131 publications

(30 citation statements)

References 32 publications

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“…Thus, increased AST may be related to oxidative stress-driven autoantigenesis in SLE [36]. This includes the oxidative modification of DNA that is detectable in circulating immune complexes of patients with SLE [37]. Thus, oxidized DNA released from the injured liver may serve as a danger signal and trigger of anti-DNA in SLE [38].…”

Section: Discussionmentioning

confidence: 99%

Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Liu

Oaks

et al. 2015

Clinical Immunology

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Liver disease (LD), defined as ≥2-fold elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT), was examined in a longitudinal study of systemic lupus erythematosus (SLE) patients. Among 435 patients, 90 (20.7%) had LD with a greater prevalence in males (15/39; 38.5%) than females (75/396; 18.9%; p = 0.01). SLE disease activity index (SLEDAI) was greater in LD patients (7.8 ± 0.7) relative to those without (5.8 ± 0.3; p = 0.0025). Anti-smooth muscle antibodies, anti-DNA antibodies, hypocomplementemia, proteinuria, leucopenia, thrombocytopenia, and anti-phospholipid syndrome were increased in LD. An absence of LD was noted in patients receiving rapamycin relative to azathioprine, cyclosporine A, or cyclophosphamide. An absence of LD was also noted in patients treated with N-acetylcysteine. LFTs were normalized and SLEDAI was diminished with increased prednisone use in 76/90 LD patients over 12.1 ± 2.6 months. Thus, LD is attributed to autoimmunity and disease activity, it responds to prednisone, and it is potentially preventable by rapamycin or N-acetylcysteine treatment.

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Section: Discussionmentioning

confidence: 99%

Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Liu

Oaks

et al. 2015

Clinical Immunology

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“…36 Autoantigens are created during cell death, typically through enzymatic cleavage, as with Ro, 36,37 or generated by oxidative modification, as for oxidized DNA. 38 Present in circulating immune complexes in patients with SLE, 39 oxidized DNA is also found in necrotic debris, which is more pro-inflammatory than apoptotic debris. 41 Indeed, in lupus-susceptible mice, systemic autoimmune disease is induced by dendritic cells that have captured necrotic but not apoptotic debris.…”

Section: Environmental Sources Of Oxidative Stressmentioning

confidence: 99%

Oxidative stress in the pathology and treatment of systemic lupus erythematosus

2013

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Oxidative stress is increased in systemic lupus erythematosus (SLE), and it contributes to immune system dysregulation, abnormal activation and processing of cell-death signals, autoantibody production and fatal comorbidities. Mitochondrial dysfunction in T cells promotes the release of highly diffusible inflammatory lipid hydroperoxides, which spread oxidative stress to other intracellular organelles and through the bloodstream. Oxidative modification of self antigens triggers autoimmunity, and the degree of such modification of serum proteins shows striking correlation with disease activity and organ damage in SLE. In T cells from patients with SLE and animal models of the disease, glutathione, the main intracellular antioxidant, is depleted and serine/threonine-protein kinase mTOR undergoes redox-dependent activation. In turn, reversal of glutathione depletion by application of its amino acid precursor, N-acetylcysteine, improves disease activity in lupus-prone mice; pilot studies in patients with SLE have yielded positive results that warrant further research. Blocking mTOR activation in T cells could conceivably provide a well-tolerated and inexpensive alternative approach to B-cell blockade and traditional immunosuppressive treatments. Nevertheless, compartmentalized oxidative stress in self-reactive T cells, B cells and phagocytic cells might serve to limit autoimmunity and its inhibition could be detrimental. Antioxidant therapy might also be useful in ameliorating damage caused by other treatments. This Review thus seeks to critically evaluate the complexity of oxidative stress and its relevance to the pathogenesis and treatment of SLE.

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“…High immunogenic potential of 8-hydroxy-2'-deoxyguanosine , the main product of oxidative DNA damage, was demonstrated [3,15]. It was also shown that DNA content of 8-OHdG in lymphocytes from patients with SLE considerably surpassed the corresponding value in healthy individuals [4], while the content of 8-OHdG in DNA of immune complexes in the plasma more that 100-fold surpassed that in nucleus DNA [12]. These facts suggest that oxidative modification of DNA can be a factor of induction of autoimmune process in SLE [4].…”

mentioning

confidence: 86%

Disturbances in hOGG1 gene expression in patients with systemic lupus erythematosus

2006

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Using the method of semiquantitative reverse transcription PCR we studied the expression of hOGG1 gene (exons 1-4 and 1-7) in peripheral blood cells from patients with systemic lupus erythematosus. Expression of this gene was disturbed in 9 of 18 patients (50%). In two patients mRNA of this gene was not expressed. In 5 patients hOGG1 mRNA was practically absent and was detected only after 35 amplification cycles. Suppression of exons 4-7 expression was detected in two of these cases and expression of both mRNA fragments (exons 1-4 and 4-7) was suppressed in 3 cases. In two patients a decrease in the relative content of exons 4-7 mRNA was found against the background of normal level of mRNA for exons 1-4. In none of the patients changes in the sequence of hOGG1 mRNA exons were revealed by parallel DGGE analysis. Our findings attest to disturbances in the expression of hOGG1 gene, primarily alpha-hOGG1 isoforms of the enzyme, in peripheral blood cells in patients with systemic lupus erythematosus.

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8‐Hydroxydeoxyguanosine

Cited by 131 publications

References 32 publications

Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Oxidative stress in the pathology and treatment of systemic lupus erythematosus

Disturbances in hOGG1 gene expression in patients with systemic lupus erythematosus

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