Palmitoylcarnitine, and important component of the repair system in the synaptosome membrane, in oxidative stress

1997 ◽  
Vol 123 (6) ◽  
pp. 565-567
Author(s):  
Yu. Yu. Tyurina ◽  
A. Arduini ◽  
V. A. Tyurin ◽  
T. V. Sokolova ◽  
E. Arrigoni-Martelli
Keyword(s):  
Oxidative Stress ◽  
Repair System ◽  
Synaptosome Membrane

Oxidative stress inactivates the human DNA mismatch repair system

2002 ◽  
Vol 283 (1) ◽  
pp. C148-C154 ◽  
Author(s):  
Christina L. Chang ◽  
Giancarlo Marra ◽  
Dharam P. Chauhan ◽  
Hannah T. Ha ◽  
Dong K. Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mismatch Repair ◽  
Chronic Inflammation ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Microsatellites ◽  
Single Base ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System

In the human DNA mismatch repair (MMR) system, hMSH2 forms the hMutSα and hMutSβ complexes with hMSH6 and hMSH3, respectively, whereas hMLH1 and hPMS2 form the hMutLα heterodimer. These complexes, together with other components in the MMR system, correct single-base mismatches and small insertion/deletion loops that occur during DNA replication. Microsatellite instability (MSI) occurs when the loops in DNA microsatellites are not corrected because of a malfunctioning MMR system. Low-frequency MSI (MSI-L) is seen in some chronically inflamed tissues in the absence of genetic inactivation of the MMR system. We hypothesize that oxidative stress associated with chronic inflammation might damage protein components of the MMR system, leading to its functional inactivation. In this study, we demonstrate that noncytotoxic levels of H2O2 inactivate both single-base mismatch and loop repair activities of the MMR system in a dose-dependent fashion. On the basis of in vitro complementation assays using recombinant MMR proteins, we show that this inactivation is most likely due to oxidative damage to hMutSα, hMutSβ, and hMutLα protein complexes. We speculate that inactivation of the MMR function in response to oxidative stress may be responsible for the MSI-L seen in nonneoplastic and cancer tissues associated with chronic inflammation.

scholarly journals Defects in the Error Prevention Oxidized Guanine System Potentiate Stationary-Phase Mutagenesis in Bacillus subtilis

2008 ◽  
Vol 191 (2) ◽  
pp. 506-513 ◽  
Author(s):  
Luz E. Vidales ◽  
Lluvia C. Cárdenas ◽  
Eduardo Robleto ◽  
Ronald E. Yasbin ◽  
Mario Pedraza-Reyes
Keyword(s):  
Oxidative Stress ◽  
Bacillus Subtilis ◽  
Stationary Phase ◽  
Repair System ◽  
Induced Mutations ◽  
General Role ◽  
Error Prevention ◽  
Repair Mechanisms ◽  
Induced Mutagenesis ◽  
Oxidized Guanine

ABSTRACT Previous studies showed that a Bacillus subtilis strain deficient in mismatch repair (MMR; encoded by the mutSL operon) promoted the production of stationary-phase-induced mutations. However, overexpression of the mutSL operon did not completely suppress this process, suggesting that additional DNA repair mechanisms are involved in the generation of stationary-phase-associated mutants in this bacterium. In agreement with this hypothesis, the results presented in this work revealed that starved B. subtilis cells lacking a functional error prevention GO (8-oxo-G) system (composed of YtkD, MutM, and YfhQ) had a dramatic propensity to increase the number of stationary-phase-induced revertants. These results strongly suggest that the occurrence of mutations is exacerbated by reactive oxygen species in nondividing cells of B. subtilis having an inactive GO system. Interestingly, overexpression of the MMR system significantly diminished the accumulation of mutations in cells deficient in the GO repair system during stationary phase. These results suggest that the MMR system plays a general role in correcting base mispairing induced by oxidative stress during stationary phase. Thus, the absence or depression of both the MMR and GO systems contributes to the production of stationary-phase mutants in B. subtilis. In conclusion, our results support the idea that oxidative stress is a mechanism that generates genetic diversity in starved cells of B. subtilis, promoting stationary-phase-induced mutagenesis in this soil microorganism.

scholarly journals Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress

2021 ◽  
Vol 9 ◽  
Author(s):  
Mariarosaria De Rosa ◽  
Samuel A. Johnson ◽  
Patricia L. Opresko
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Genome Stability ◽  
Repair System ◽  
Telomeric Dna ◽  
Telomere Shortening ◽  
Guanine Oxidation ◽  
Repeat Sequences ◽  
Human Reproductive ◽  
Base Lesion

Telomeres are protective nucleoprotein structures that cap linear chromosome ends and safeguard genome stability. Progressive telomere shortening at each somatic cell division eventually leads to critically short and dysfunctional telomeres, which can contribute to either cellular senescence and aging, or tumorigenesis. Human reproductive cells, some stem cells, and most cancer cells, express the enzyme telomerase to restore telomeric DNA. Numerous studies have shown that oxidative stress caused by excess reactive oxygen species is associated with accelerated telomere shortening and dysfunction. Telomeric repeat sequences are remarkably susceptible to oxidative damage and are preferred sites for the production of the mutagenic base lesion 8-oxoguanine, which can alter telomere length homeostasis and integrity. Therefore, knowledge of the repair pathways involved in the processing of 8-oxoguanine at telomeres is important for advancing understanding of the pathogenesis of degenerative diseases and cancer associated with telomere instability. The highly conserved guanine oxidation (GO) system involves three specialized enzymes that initiate distinct pathways to specifically mitigate the adverse effects of 8-oxoguanine. Here we introduce the GO system and review the studies focused on investigating how telomeric 8-oxoguanine processing affects telomere integrity and overall genome stability. We also discuss newly developed technologies that target oxidative damage selectively to telomeres to investigate roles for the GO system in telomere stability.

scholarly journals Mycobacterium bovis BCG recADeletion Mutant Shows Increased Susceptibility to DNA-Damaging Agents but Wild-Type Survival in a Mouse Infection Model

2001 ◽  
Vol 69 (6) ◽  
pp. 3562-3568 ◽  
Author(s):  
Peter Sander ◽  
K. G. Papavinasasundaram ◽  
Thomas Dick ◽  
Evangelos Stavropoulos ◽  
Kerstin Ellrott ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Mycobacterium Bovis ◽  
Defense Mechanisms ◽  
Reactive Oxygen ◽  
Infection Model ◽  
Repair System ◽  
Mouse Infection Model ◽  
Dna Damaging Agents ◽  
Increased Susceptibility

ABSTRACT Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxifies reactive oxygen species, and DNA repair systems, which repair damage resulting from oxidative stress. To (i) determine the relative importance of the DNA repair system when oxidative stress is encountered by theMycobacterium tuberculosis complex during infection of the host and to (ii) provide improved mycobacterial hosts as live carriers to express foreign antigens, the recA locus was inactivated by allelic exchange in Mycobacterium bovisBCG. The recA mutants are sensitive to DNA-damaging agents and show increased susceptibility to metronidazole, the first lead compound active against the dormant M. tuberculosis complex. Surprisingly, the recAgenotype does not affect the in vitro dormancy response, nor does the defect in the DNA repair system lead to attenuation as determined in a mouse infection model. The recA mutants will be a valuable tool for further development of BCG as an antigen delivery system to express foreign antigens and as a source of a genetically stable vaccine against tuberculosis.

Baicalein (5,6,7-trihydroxyflavone) reduces oxidative stress-induced DNA damage by upregulating the DNA repair system

2012 ◽  
Vol 28 (6) ◽  
pp. 421-433 ◽  
Author(s):  
Ki Cheon Kim ◽  
In Kyung Lee ◽  
Kyoung Ah Kang ◽  
Hye Sun Kim ◽  
Sam Sik Kang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Repair System

scholarly journals Characteristic mutations induced in the small intestine of Msh2-knockout gpt delta mice

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Yasunobu Aoki ◽  
Mizuki Ohno ◽  
Michiyo Matsumoto ◽  
Michi Matsumoto ◽  
Kenichi Masumura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Small Intestine ◽  
Mismatch Repair ◽  
Spontaneous Mutation ◽  
Potassium Bromate ◽  
Repair System ◽  
Mismatch Repair Deficiency ◽  
Single Base ◽  
Repair Deficiency ◽  
Mutant Frequency

Abstract Background Base pair mismatches in genomic DNA can result in mutagenesis, and consequently in tumorigenesis. To investigate how mismatch repair deficiency increases mutagenicity under oxidative stress, we examined the type and frequency of mutations arising in the mucosa of the small intestine of mice carrying a reporter gene encoding guanine phosphoribosyltransferase (gpt) and in which the Msh2 gene, which encodes a component of the mismatch repair system, was either intact (Msh2+/+::gpt/0; Msh2-bearing) or homozygously knockout (KO) (Msh2−/−::gpt/0; Msh2-KO). Results Gpt mutant frequency in the small intestine of Msh2-KO mice was about 10 times that in Msh2-bearing mice. Mutant frequency in the Msh2-KO mice was not further enhanced by administration of potassium bromate, an oxidative stress inducer, in the drinking water at a dose of 1.5 g/L for 28 days. Mutation analysis showed that the characteristic mutation in the small intestine of the Msh2-KO mice was G-to-A transition, irrespective of whether potassium bromate was administered. Furthermore, administration of potassium bromate induced mutations at specific sites in gpt in the Msh2-KO mice: G-to-A transition was frequently induced at two known sites of spontaneous mutation (nucleotides 110 and 115, CpG sites) and at nucleotides 92 and 113 (3′-side of 5′-GpG-3′), and these sites were confirmed to be mutation hotspots in potassium bromate-administered Msh2-KO mice. Administration of potassium bromate also induced characteristic mutations, mainly single-base deletion and insertion of an adenine residue, in sequences of three to five adenine nucleotides (A-runs) in Msh2-KO mice, and elevated the overall proportion of single-base deletions plus insertions in Msh2-KO mice. Conclusions Our previous study revealed that administration of potassium bromate enhanced tumorigenesis in the small intestine of Msh2-KO mice and induced G-to-A transition in the Ctnnb1 gene. Based on our present and previous observations, we propose that oxidative stress under conditions of mismatch repair deficiency accelerates the induction of single-adenine deletions at specific sites in oncogenes, which enhances tumorigenesis in a synergistic manner with G-to-A transition in other oncogenes (e.g., Ctnnb1).

scholarly journals Dissecting the Molecular Response of Human Escs to Iron-Mediated Oxidative Stress by Genetic Silencing of FTH1 Gene

2021 ◽  
Author(s):  
Luana Scaramuzzino ◽  
Valeria Lucchino ◽  
Stefania Scalise ◽  
Michela Lo Conte ◽  
Clara Zannino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Embryoid Bodies ◽  
Repair System ◽  
Nuclear Factor ◽  
Human Escs ◽  
Iron Storage ◽  
Nrf2 Pathway ◽  
Nrf2 Signaling Pathway

Abstract Background: Embryonic stem cells (ESCs) are pluripotent cells with indefinite self-renewal ability and differentiation properties. As such, to function properly and maintain genomic stability, ESCs need to be endowed with an efficient repair system as well as effective redox homeostasis. In this study, we investigated and characterized different aspects involved in ESCs response to iron accumulation following stable knockdown of ferritin heavy chain (FTH1) gene, encoding for a major iron storage protein with ferroxidase activity. Methods: stable FTH1 knockdown of H9-hES cell line was achieved with the use of shRNA lentiviral particles. Upon FTH1 silencing, we speculated whether hESCs still retained their pluripotency capability were first monitored for their capability the pluripotent status,FTH1 stable knock-down ESCs were obtained using lentiviral vector plasmids. The effect of FTH1 silencing on hESCs pluripotency was evaluated through alkaline phosphatase (AP) staining, immunofluorescence and embryoid bodies (EBs) formation assay. Western blotting and qRT-PCR analysis were performed to assess the involvement of nuclear factor (erythroid-derived-2)-like 2 (Nrf2) and pentose phosphate pathway (PPP) in the antioxidant response. ROS levels and mitochondrial functionality were explored by flow cytometry. Seahorse Analyzer was used to evaluate metabolic and bioenergetic profiles. Results: Our findings clearly show that FTH1 silencing in hESCs does not correlate with increased ROS production nor with redox status strengthening the concept that hESCs are extremely resistant and, to certain extent, even refractory to the pattern of results produced in other cell lines. Collectively, our results demonstrate that FTH1 silencing is accompanied by a significant activation of the nuclear factor (erythroid-derived-2)-like 2 (Nrf2) signaling pathway and pentose phosphate pathway (PPP) which crosstalk in driving hESCs antioxidant cascade events able to antagonize the effects of FTH1 silencing.Conclusion: to our knowledge, this is the first evidence of a crosstalk between FTH1 silencing and Nrf2 pathway activation in hESCs, casting a new light on how human ESCs perform under oxidative stress conditions. Our findings go beyond previous reports, showing how the Nrf2 pathway, in combination with PPP activation, regulates the molecular signature underlying ESCs defence mechanisms against oxidative stress mediated by FTH1 downregulation.

UCTD and SLE patients show increased levels of oxidative and DNA damage together with an altered kinetics of DSB repair

Mutagenesis ◽  
2021 ◽  
Author(s):  
Consuelo Micheli ◽  
Alice Parma ◽  
Chiara Tani ◽  
Domenica Di Bello ◽  
Aurora Falaschi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Disease Activity ◽  
Treatment Plan ◽  
Connective Tissue Diseases ◽  
Autoimmune Disorders ◽  
Control Group ◽  
Repair System ◽  
Serological Profile ◽  
Genome Damage

Abstract Immunological tolerance is a critical feature of the immune system; its loss might lead to an abnormal response of lymphocytes causing autoimmune diseases. One of the most important groups belonging to autoimmune disorders is the connective tissue diseases (CTD). CTD are classified among systemic rheumatic diseases and include pathologies such as systemic lupus erythematosus (SLE), and undifferentiated CTD (UCTD). In this study, we evaluated oxidative and genome damage in peripheral blood lymphocytes from patients with SLE and UCTD, further classified on the basis of disease activity and the presence/absence of a serological profile. Oxidative damage was evaluated in cell membrane using the fluorescent fatty acid analogue BODIPY 581/591 C11. The percentage of oxidised lymphocytes in both SLE and UCTD patients was higher than in the control group, and the oxidative stress correlated positively with both disease activity and autoantibody profile. The γH2AX focus assay was used to quantify the presence of spontaneous double strand breaks (DSBs), and to assess the abilities of DSBs repair system after T cells were treated with mitomycin C (MMC). Subjects with these autoimmune disorders showed a higher number of γH2AX foci than healthy controls, but no correlation with diseases activity and presence of serological profile was observed. In addition, patients displayed an altered response to MMC-induced DSBs, which led their peripheral cells to greatly increase apoptosis. Taken together our results confirmed an interplay among oxidative stress, DNA damage and impaired DNA repair, which are directly correlated to the aggressiveness and clinical progression of the diseases. We propose the evaluation of these molecular markers to better characterize SLE and UCTD, aiming to improve the treatment plan and the quality of the patients’ life.

scholarly journals Indices of the DNA repair system in the brain of fish as a biomarker of inorganic mercury burden

2021 ◽  
Vol 32 (1) ◽  
pp. 9-16
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
R. O. Novitskyi ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Environmental Pollution ◽  
Dose Range ◽  
Inorganic Mercury ◽  
Mercury Chloride ◽  
Repair System ◽  
Fish Brain ◽  
Low Concentrations ◽  
The Brain

Mercury is a widespread heavy metal that causes a stable and prolonged environmental pollution. Low concentrations of inorganic and organic mercury compounds are found in almost all water bodies. The high level of mercury bioaccumulation is a cause of tissue-specific toxicity, including neurotoxicity. Absorbed in nervous tissue mercury can cause brain disorders both in neural and glial cells. The brain of fish is considered one of the most susceptible targets for cytotoxicity of mercury in aquatic ecosystems. Taking into account that different forms of mercury have widespread distribution and exhibit a strong neurotoxic effect, the assessment of mercury cytotoxicity in the brain of fish is relevant and extremely important. Rainbow trout Oncorhynchus mykiss was exposed to mercury chloride in the dose range of 5-20 μg/L for 60 days to study the chronic exposure of low doses. In this paper, we studied the influence of inorganic mercury on oxidative stress, DNA repair proteins – ERCC1 and PARP1 in the trout’s brain. The results obtained have shown that the chronic effect of inorganic mercury causes dose-dependent oxidative stress in the fish brain. In addition, low concentrations of mercury (10 and 20 μg/L) caused a decrease in the content of ERCC1 in the brain of fish. On the contrary, the same doses have caused an increase in PARP1 expression. That is the chronic influence of low concentrations of inorganic mercury has a negative effect in the fish brain. Observed results showed that inorganic mercury has a potential for suppressing DNA repair and, therefore, increases the instability of genome. Thus, ERCC1 and PARP1 can be considered as the sensitive biomarkers of mercury cytotoxicity in the fish brain. A further study of mercury neurotoxicity is needed to find out the hazard of mercury environmental pollution as well as a validation of biomarkers of their impact.

Sign in / Sign up

Export Citation Format

Share Document