Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydralazine caused site-specific DNA damage in the presence of Cu(II), Co(II), Fe(III), or peroxidase/H2O2. The order of inducing effect of metal ions on hydralazine-dependent DNA damage [Cu(II) greater than Co(II) greater than Fe(III)] was related to that of accelerating effect on the O2 consumption rate of hydralazine autoxidation. Catalase completely inhibited DNA damage by hydralazine plus Cu(II), but hydroxyl radical (.OH) scavengers and superoxide dismutase did not. On the other hand, DNA damage by hydralazine plus Fe(III) was inhibited by catalase and .OH scavengers. Hydralazine plus Cu(II) induced piperidine-labile sites predominantly at guanine and some adenine residues, whereas hydralazine plus Fe(III) caused cleavages at every nucleotide. Activation of hydralazine by peroxidase/H2O2 caused guanine-specific modification in DNA. ESR-spin trapping experiment showed that .OH and superoxide are generated during the Fe(III)- or Cu(II)-catalysed autoxidation of hydralazine, respectively, and that nitrogen-centered radical is generated during the Cu(II)- or peroxidase-catalysed oxidation. The generation of nitrogen-centered radical was also supported by HPLC-mass spectrometry. The results suggest that the guanine-specific modification by the enzymatic activation of hydralazine is due to the nitrogen-centered hydralazyl radical or derived active species, whereas .OH participates in DNA damage by hydralazine plus Fe(III). The mechanism of hydralazine plus Cu(II)-induced DNA damage is complex. The possible role of the DNA damage induced by hydralazine in the presence of Cu(II) or peroxidase/H2O2 is discussed in relation to hydralazine-induced lupus, mutation, and cancer.
 ...
PMID:Free radical production and site-specific DNA damage induced by hydralazine in the presence of metal ions or peroxidase/hydrogen peroxide. 184 78

Catalase (CAT) and peroxisome proliferator activated receptor-gamma2 (PPARgamma2) are important regulators of oxidative stress and inflammation, which may contribute to the development of systemic lupus erythematosus (SLE). The objective of this study was to investigate the effects of genetic polymorphisms of CAT and PPARy2 on risk and severity of SLE in a Korean population. DNA was isolated from blood samples collected from 345 patients with SLE and 400 controls. Genotyping for the -262C-->T polymorphism of CAT and the Pro 12Ala polymorphism of PPARgamma2 were performed by PCR-RFLP analysis. The severity of SLE was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). No association was observed between genotypes for any of the clinical manifestations of SLE. CAT and PPARgamma2 genotypes were not associated with either risk or severity of SLE. For subjects who were carriers of the high activity T allele for CAT and have the Pro/Pro genotype for PPARgamma2, the odds ratio (95% confidence interval) for risk of SLE was 0.45 (0.23-1.08). Our results suggest that genetic polymorphisms of CAT and PPARy2 do not play a significant role in the development of SLE in a Korean population. A possible protective effect of a combined genotype warrants further investigation.
Lupus 2005
PMID:Catalase and PPARgamma2 genotype and risk of systemic lupus erythematosus in Koreans. 1593 34