Limits...
DNA damage in rheumatoid arthritis: an age-dependent increase in the lipid peroxidation-derived DNA adduct, heptanone-etheno-2'-deoxycytidine.

Ogawa M, Matsuda T, Ogata A, Hamasaki T, Kumanogoh A, Toyofuku T, Tanaka T - Autoimmune Dis (2013)

Bottom Line: Results.H ε dC levels correlated well with the number of swollen joints (r = 0.57, P < 0.0001) and weakly with the number of tender joints (r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan.

ABSTRACT
Objective. To evaluate what types of DNA damages are detected in rheumatoid arthritis (RA). Methods. The DNA adducts such as 8-oxo-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), 1,N(6)-etheno-2'-deoxyadenosine ( ε dA), and heptanone-etheno-2'-deoxycytidine (H ε dC) in genomic DNAs, derived from whole blood cells from 46 RA patients and 31 healthy controls, were analyzed by high-performance liquid chromatography tandem mass spectrometry, and their levels in RA patients and controls were compared. In addition, correlation between DNA adducts and clinical parameters of RA was analyzed. Results. Compared with controls, the levels of H ε dC in RA were significantly higher (P < 0.0001) and age dependent (r = 0.43, P < 0.01), while there was no significant difference in 8-oxo-dG and ε dA accumulation between RA patients and controls. H ε dC levels correlated well with the number of swollen joints (r = 0.57, P < 0.0001) and weakly with the number of tender joints (r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3. Conclusion. These findings indicate that H ε dC may have some influence on the development of RA and/or its complications.

No MeSH data available.


Related in: MedlinePlus

Chemical structures of DNA adducts and their corresponding peaks detected by LC-MS/MS. (a) Chemical structures of the DNA adducts 8-oxo-hydroxy-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), 1,N6-etheno-2′-deoxyadenosine (εdA), and heptanone-etheno-2′-deoxycytidine (HεdC). (b) DNA adducts were quantified by calculating the ratio of the peak of the DNA adduct to that of its standard isotope. The respective peaks of the standard isotope and the corresponding sample are shown.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3814043&req=5

fig1: Chemical structures of DNA adducts and their corresponding peaks detected by LC-MS/MS. (a) Chemical structures of the DNA adducts 8-oxo-hydroxy-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), 1,N6-etheno-2′-deoxyadenosine (εdA), and heptanone-etheno-2′-deoxycytidine (HεdC). (b) DNA adducts were quantified by calculating the ratio of the peak of the DNA adduct to that of its standard isotope. The respective peaks of the standard isotope and the corresponding sample are shown.

Mentions: Values for the three DNA adducts, 8-oxo-dG, εdA, and HεdC, were assessed and their chemical structures are shown in Figure 1(a). The 4-ONE DNA adduct HεdC was synthesized according to the previously published methods [13]. 8-oxo-dG and εdA were obtained from Sigma Aldrich Japan. [U-15N5]-8-oxo-dG was kindly provided by Dr. Shinya Shibutani, State University of New York, Stony Brook, NY, USA, and other DNA adduct stable isotope standards were synthesized according to the previously described methods [12] using [U-15N5]- or [U-15N3]-deoxynucleoside purchased from Cambridge Isotope Laboratories (Andover, MA, USA).


DNA damage in rheumatoid arthritis: an age-dependent increase in the lipid peroxidation-derived DNA adduct, heptanone-etheno-2'-deoxycytidine.

Ogawa M, Matsuda T, Ogata A, Hamasaki T, Kumanogoh A, Toyofuku T, Tanaka T - Autoimmune Dis (2013)

Chemical structures of DNA adducts and their corresponding peaks detected by LC-MS/MS. (a) Chemical structures of the DNA adducts 8-oxo-hydroxy-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), 1,N6-etheno-2′-deoxyadenosine (εdA), and heptanone-etheno-2′-deoxycytidine (HεdC). (b) DNA adducts were quantified by calculating the ratio of the peak of the DNA adduct to that of its standard isotope. The respective peaks of the standard isotope and the corresponding sample are shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814043&req=5

fig1: Chemical structures of DNA adducts and their corresponding peaks detected by LC-MS/MS. (a) Chemical structures of the DNA adducts 8-oxo-hydroxy-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), 1,N6-etheno-2′-deoxyadenosine (εdA), and heptanone-etheno-2′-deoxycytidine (HεdC). (b) DNA adducts were quantified by calculating the ratio of the peak of the DNA adduct to that of its standard isotope. The respective peaks of the standard isotope and the corresponding sample are shown.
Mentions: Values for the three DNA adducts, 8-oxo-dG, εdA, and HεdC, were assessed and their chemical structures are shown in Figure 1(a). The 4-ONE DNA adduct HεdC was synthesized according to the previously published methods [13]. 8-oxo-dG and εdA were obtained from Sigma Aldrich Japan. [U-15N5]-8-oxo-dG was kindly provided by Dr. Shinya Shibutani, State University of New York, Stony Brook, NY, USA, and other DNA adduct stable isotope standards were synthesized according to the previously described methods [12] using [U-15N5]- or [U-15N3]-deoxynucleoside purchased from Cambridge Isotope Laboratories (Andover, MA, USA).

Bottom Line: Results.H ε dC levels correlated well with the number of swollen joints (r = 0.57, P < 0.0001) and weakly with the number of tender joints (r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan.

ABSTRACT
Objective. To evaluate what types of DNA damages are detected in rheumatoid arthritis (RA). Methods. The DNA adducts such as 8-oxo-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), 1,N(6)-etheno-2'-deoxyadenosine ( ε dA), and heptanone-etheno-2'-deoxycytidine (H ε dC) in genomic DNAs, derived from whole blood cells from 46 RA patients and 31 healthy controls, were analyzed by high-performance liquid chromatography tandem mass spectrometry, and their levels in RA patients and controls were compared. In addition, correlation between DNA adducts and clinical parameters of RA was analyzed. Results. Compared with controls, the levels of H ε dC in RA were significantly higher (P < 0.0001) and age dependent (r = 0.43, P < 0.01), while there was no significant difference in 8-oxo-dG and ε dA accumulation between RA patients and controls. H ε dC levels correlated well with the number of swollen joints (r = 0.57, P < 0.0001) and weakly with the number of tender joints (r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3. Conclusion. These findings indicate that H ε dC may have some influence on the development of RA and/or its complications.

No MeSH data available.


Related in: MedlinePlus