scholarly journals On the irrelevancy of hydroxyl radical to DNA damage from oxidative stress and implications for epigenetics

2020 ◽  
Vol 49 (18) ◽  
pp. 6524-6528 ◽  
Author(s):  
Aaron M. Fleming ◽  
Cynthia J. Burrows

Carbonate radical anion, not hydroxyl radical, is the principal reactive oxygen species generated from endogenous oxidative stress endowing epigenetic features to guanine oxidation products in DNA.

2020 ◽  
Vol 56 (68) ◽  
pp. 9779-9782 ◽  
Author(s):  
Aaron M. Fleming ◽  
Cynthia J. Burrows

Fe(ii)-Fenton reaction in bicarbonate buffer yields CO3˙−, not HO˙, oxidizing 2′-deoxyguanosine to yield 8-oxo-7,8-dihydro-2′-deoxyguanosine with no ribose damage.


2018 ◽  
Vol 30 (1) ◽  
pp. 174
Author(s):  
Y.-J. Niu ◽  
N.-H. Kim ◽  
X.-S. Cui

C-Phycocyanin (CP) is a biliprotein enriched in blue-green algae that is known to possess antioxidant, anti-apoptosis, anti-inflammatory, and radical-scavenging properties in somatic cells. However, the protective effect of CP on porcine embryo developmental competence in vitro remains unclear. In the present study, we investigated the effect of CP on the development of porcine early embryos as well as its underlying mechanisms exposing them to H2O2 to induce oxidative stress. The levels of reactive oxygen species, mitochondrial membrane potential, apoptosis, DNA damage, and autophagy in the blastocysts were observed by staining with 2′,7′-dichlorodihydrofluorescein diacetate (H2DCF-DA), 5,5′,6,6’-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1), terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate (dUTP) nick-end labelling (TUNEL), anti-cytochrome c, and anti-γH2A.X (Ser139), respectively. Colocalization assay of mitochondria and cytochrome c of blastocysts were staining with MitoTracker Red CMXRos and anti-cytochrome c. All data were subjected to one-way ANOVA. Different concentrations of CP (1, 2, 5, 8, 10 µg mL−1) were added to porcine zygote medium 5 (PZM-5, l-glutamine concentration of PZM-3 was modified from 1 to 2 mM) during in vitro culture. The results showed that 5 µg mL−1 CP significantly increased blastocyst formation (62.5 ± 2.1 v. 52.7 ± 2.4; P < 0.05) and hatching rate (10.9 ± 1.9 v. 36.6 ± 5.2; P < 0.05) compared with controls. Blastocyst formation (53.1 ± 2.3 v. 40.1 ± 2.3; P < 0.05) and quality were significantly increased in the 50 µM H2O2 treatment group following 5 µg mL−1 CP addition. C-Phycocyanin prevented the H2O2-induced compromise of mitochondrial membrane potential, release of cytochrome c from the mitochondria, and generation of reactive oxygen species. Furthermore, apoptosis, DNA damage level, and autophagy in the blastocysts were attenuated by supplementation of CP in the H2O2-induced oxidative injury group compared with that in controls. These results suggest that CP has beneficial effects on the development of porcine parthenotes by attenuating mitochondrial dysfunction and oxidative stress.


2021 ◽  
Vol 18 (7) ◽  
pp. 603-618
Author(s):  
Xue Xin Goh ◽  
Pek Yee Tang ◽  
Shiau Foon Tee

Objective Mental illnesses may be caused by genetic and environmental factors. Recent studies reported that mental illnesses were accompanied by higher oxidative stress level. However, the results were inconsistent. Thus, present meta-analysis aimed to analyse the association between oxidative DNA damage indicated by 8-hydroxy-2’-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), which has been widely used as biomarker of oxidative stress, and mental illnesses, including schizophrenia, bipolar disorder and depression. As oxidative DNA damage is caused by reactive oxygen species (ROS), systematic review and meta-analysis were also conducted to analyse the relationship between ROS and these three mental illnesses.Methods Studies from 1964 to 2020 (for oxidative DNA damage) and from 1907 to 2021 (for ROS) in Pubmed and Scopus databases were selected and analysed using Comprehensive Meta-Analysis version 2 respectively. Data were subjected to meta-analysis for examining the effect sizes of the results. Publication bias assessments, heterogeneity assessments and subgroup analyses based on biological specimens, patient status, illness duration and medication history were also conducted.Results This meta-analysis revealed that oxidative DNA damage was significantly higher in patients with schizophrenia and bipolar disorder based on random-effects models whereas in depressed patients, the level was not significant. Since heterogeneity was present, results based on random-effects model was preferred. Our results also showed that oxidative DNA damage level was significantly higher in lymphocyte and urine of patients with schizophrenia and bipolar disorder respectively. Besides, larger effect size was observed in inpatients and those with longer illness duration and medication history. Significant higher ROS was also observed in schizophrenic patients but not in depressive patients.Conclusion The present meta-analysis found that oxidative DNA damage was significantly higher in schizophrenia and bipolar disorder but not in depression. The significant association between deoxyguanosines and mental illnesses suggested the possibility of using 8-OHdG or 8-oxodG as biomarker in measurement of oxidative DNA damage and oxidative stress. Higher ROS level indicated the involvement of oxidative stress in schizophrenia. The information from this study may provide better understanding on pathophysiology of mental illnesses.


2018 ◽  
Vol 121 ◽  
pp. 180-189 ◽  
Author(s):  
Brock Matter ◽  
Christopher L. Seiler ◽  
Kristopher Murphy ◽  
Xun Ming ◽  
Jianwei Zhao ◽  
...  

2020 ◽  
Author(s):  
Xianpeng Ge ◽  
Lizhi He ◽  
Haibo Liu ◽  
Cole M. Haynes ◽  
Jae-Hyuck Shim

AbstractThe endocytic pathway actively interacts with mitochondria in maintaining cellular homeostasis. However, how the dysfunction of this inter-organelle interaction causing pathological outcomes remains less understood. Here we show that an aberrant endocytic pathway from the deficiency of CHMP5 in skeletal progenitor cells causes accumulation of functionally compromised mitochondria, which induce cellular senescence via reactive oxygen species (ROS)-mediated oxidative stress and DNA damage. These senescent progenitors can lead to distorted skeletal growth via a combination of cell-autonomous and non-autonomous mechanisms. Consequently, mice lacking Chmp5 in Ctsk-expressing periskeletal progenitors or Dmp1-expressing musculoskeletal progenitors develop multiple skeletal/muscular abnormalities, including robust bone overgrowth, progressive joint stiffness, and myopathy. Targeting senescent cells using senolytic drugs significantly alleviates these lesions and improves animal motility. Overall, our results reveal that CHMP5 restricts skeletal progenitor cell senescence through maintaining the endo-lysosomal-mitochondrial network and cell senescence represents a yet unexplored mechanism for detrimental alterations from the perturbed organelle network.


1997 ◽  
Vol 8 (11) ◽  
pp. 1722-1731 ◽  
Author(s):  
W Gwinner ◽  
U Landmesser ◽  
R P Brandes ◽  
B Kubat ◽  
J Plasger ◽  
...  

Results from several radical scavenger studies indirectly suggested an involvement of reactive oxygen species in the pathogenesis of puromycin aminonucleoside glomerulopathy. In this study, generation of reactive oxygen species was examined directly in glomeruli isolated from rats in the acute phase of puromycin aminonucleoside nephrosis and related to the changes in the glomerular antioxidant defense. Five and nine days after puromycin aminonucleoside injection, gross proteinuria, reduced creatinine clearances, and typical changes of glomerular morphology were present. Levels of reactive oxygen species were increased eightfold in glomeruli isolated 15 min after puromycin aminonucleoside injection, returned to baseline levels on days 1 and 5 after injection, and rose again to 14-fold on day 9 after injection, as determined by chemiluminescence with luminol. Further analysis of increased glomerular radical generation, using the chemiluminescence enhancer lucigenin and different radical scavengers, suggested a predominant involvement of hydroxyl radical and hydrogen peroxide in the initial increase in reactive oxygen species 15 min after puromycin aminonucleoside. Nine days after induction of nephrosis, primarily superoxide anion and hydroxyl radical were found to contribute to increased reactive oxygen species. Despite oxidative stress, antioxidant enzymes were not induced in the course of nephrosis. On the contrary, catalase and glutathione peroxidase activities declined 9 d after puromycin aminonucleoside injection. The results indicate that a transient increase in glomerular reactive oxygen species is sufficient to induce the oxidative glomerular injury observed in this model and that the glomerulus may not necessarily respond to oxidative stress with an induction of antioxidant enzymes.


2021 ◽  
Author(s):  
Barry Halliwell ◽  
Amitava Adhikary ◽  
Michael Dingfelder ◽  
Miral Dizdaroglu

Schematic representation of the important chemical reactions involved in reactive oxygen species-mediated DNA damage.


2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Justyna Mikuła-Pietrasik ◽  
Patrycja Sosińska ◽  
Marek Murias ◽  
Marcin Wierzchowski ◽  
Marta Brewińska-Olchowik ◽  
...  

We explored the effect of a new resveratrol (RVT) derivative, 3,3′,4,4′-tetrahydroxy-trans-stilbene (3,3′,4,4′-THS), on viability, apoptosis, proliferation, and senescence of three representative lines of ovarian cancer cells, that is, A2780, OVCAR-3, and SKOV-3,in vitro. In addition, the mechanistic aspects of 3,3′,4,4′-THS activity, including cell redox homeostasis (the production of reactive oxygen species, activity of enzymatic antioxidants, and magnitude of DNA damage accumulation and repair), and the activity of caspases (3, 8, and 9) and p38 MAPK were examined. The study showed that 3,3′,4,4′-THS affects cancer cell viability much more efficiently than its parent drug. This effect coincided with increased generation of reactive oxygen species, downregulated activity of superoxide dismutase and catalase, and excessive accumulation of 8-hydroxy-2′-deoxyguanosine and its insufficient repair due to decreased expression of DNA glycosylase I. Cytotoxicity elicited by 3,3′,4,4′-THS was related to increased incidence of apoptosis, which was mediated by caspases 3 and 9. Moreover, 3,3′,4,4′-THS inhibited cancer cell proliferation and accelerated senescence, which was accompanied by the activation of p38 MAPK. Collectively, our findings indicate that 3,3′,4,4′-THS may constitute a valuable tool in the fight against ovarian malignancy and that the anticancer capabilities of this stilbene proceed in an oxidative stress-dependent mechanism.


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