Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P16104 (H2AX)
 3,930 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, cellular redox environment gained significant attention as a critical regulator of cellular responses to oxidative stress. Cellular redox environment is a balance between production of reactive oxygen species and their removal by antioxidant enzymes. We investigated the hypothesis that mitochondrial antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells. Vector-control and manganese superoxide dismutase (MnSOD) overexpressing human pancreatic cancer cells were irradiated and assayed for cell survival and activation of the G(2)-checkpoint pathway. Increased MnSOD activity significantly increased cell survival following irradiation with 6 Gy of gamma-radiation (p < 0.05). The MnSOD overexpressing irradiated cells also revealed 3-4 folds increase in the percentage of G(2) cells compared to irradiated vector-control. Furthermore, MnSOD overexpressing irradiated cells exhibited increased loss of phosphorylated histone H2AX protein levels. The radiation-induced increase in cyclin B1 protein levels in irradiated vector-control cells was suppressed in irradiated MnSOD overexpressing cells. Mitochondria-targeted catalase overexpression increased the survival of irradiated cells. These results support the hypothesis that mitochondrial antioxidant enzyme activity and mitochondria-generated reactive oxygen species-signaling (superoxide and hydrogen peroxide) could regulate radiation-induced G(2) checkpoint activation and radioresistance in human pancreatic cancer cells.
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PMID:Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells. 1849 75

Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of alpha-particle irradiation, the fraction of gamma-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy alpha-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H(2)O(2)), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress.
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PMID:Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors. 1864 Jan 33

We elucidated the cytoprotective effects of hyperoside (quercetin-3-O-galactoside) against hydrogen peroxide (H2O2)-induced cell damage. We found that hyperoside scavenged the intracellular reactive oxygen species (ROS) detected by fluorescence spectrometry, flow cytometry, and confocal microscopy. In addition, we found that hyperoside scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4)+H2O2) in a cell-free system, which was detected by electron spin resonance (ESR) spectrometry. Hyperoside was found to inhibit H2O2-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA fragmentation. In addition, hyperoside pretreatment inhibited the H2O2-induced activation of caspase-3 measured in terms of levels of cleaved caspase-3. Hyperoside prevented H2O2-induced lipid peroxidation as well as protein carbonyl. In addition, hyperoside prevented the H2O2-induced cellular DNA damage, which was established by comet tail, and phospho histone H2A.X expression. Furthermore, hyperoside increased the catalase and glutathione peroxidase activities. Conversely, the catalase inhibitor abolished the cytoprotective effect of hyperoside from H2O2-induced cell damage. In conclusion, hyperoside was shown to possess cytoprotective properties against oxidative stress by scavenging intracellular ROS and enhancing antioxidant enzyme activity.
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PMID:Hyperoside prevents oxidative damage induced by hydrogen peroxide in lung fibroblast cells via an antioxidant effect. 1876 93

Flavonoids are a class of secondary metabolites abundantly found in fruits and vegetables. In addition, flavonoids have been reported as potent antioxidants with beneficial effects against oxidative stress-related diseases such as cancer, aging, and diabetes. The present study was carried out to investigate the cytoprotective effects of morin (2',3,4',5,7-pentahydroxyflavone), a member of the flavonoid group, against hydrogen peroxide (H(2)O(2))-induced DNA and lipid damage. Morin was found to prevent the cellular DNA damage induced by H(2)O(2) treatment, which is shown by the inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation (a modified form of DNA base), inhibition of comet tail (a form of DNA strand breakage), and decrease of nuclear phospho histone H2A.X expression (a marker for DNA strand breakage). In addition, morin inhibited membrane lipid peroxidation, which is detected by inhibition of thiobarbituric acid reactive substance (TBARS) formation. Morin was found to scavenge the intracellular reactive oxygen species (ROS) generated by H(2)O(2) treatment in cells, which is detected by a spectrofluorometer, flow cytometry, and confocal microscopy after staining of 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA). Morin also induces an increase in the activity of catalase and protein expression. The results of this study suggest that morin protects cells from H(2)O(2)-induced damage by inhibiting ROS generation and by inducing catalase activation.
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PMID:Cellular protection of morin against the oxidative stress induced by hydrogen peroxide. 1879 23

We elucidated the protective effect of 7,8-dihydroxyflavone against hydrogen peroxide (H(2)O(2))-induced DNA damage. We found that 7,8-dihydroxyflavone scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and intracellular reactive oxygen species (ROS). 7,8-Dihydroxyflavone with antioxidant effect prevented the H(2)O(2)-induced cellular DNA damage, as evidenced by comet tail, 8-hydroxy-2'-deoxyguanosine (8-OHdG) content, and phospho-histone H2A.X protein expression. Hence, 7,8-dihydroxyflavone was shown to protect cell via the inhibition of apoptosis induced by H(2)O(2). This was substantiated by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA fragmentation. Furthermore, 7,8-dihydroxyflavone activated the protein kinase B (PKB, Akt) signal pathway, which is a major survival signal pathway. In addition, LY294002, which is phosphatidylinositol 3 kinase (PI3K, upstream of Akt) inhibitor, attenuated the protective effect of 7,8-dihydroxyflavone against H(2)O(2)-induced cell damage. In conclusion, 7,8-dihydroxyflavone was shown to possess cytoprotective properties against oxidative stress by scavenging intracellular ROS and enhancing Akt activity.
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PMID:Preventive effect of 7,8-dihydroxyflavone against oxidative stress induced genotoxicity. 1918 70

DNA double-strand breaks (DSBs) are considered as one of the primary causes of cancer but their induction by hydrogen peroxide (H(2)O(2)) is still controversial. In this work, we studied whether the high levels of H(2)O(2) produced in the thyroid to oxidize iodide could induce DNA modifications. Scores of DNA damage, in terms of strand breaks, were obtained by comet assay (alkaline condition for single-strand breaks (SSBs) and neutral condition for DSBs). We demonstrated that in a rat thyroid cell line (PCCl3), non-lethal concentrations of H(2)O(2) (0.1-0.5 mmol/l) as well as irradiation (1-10 Gy) provoked a large number of SSBs ( approximately 2-3 times control DNA damage values) but also high levels of DSBs (1.2-2.3 times control DNA damage values). We confirmed the generation of DSBs in this cell line and also in human thyroid in primary culture and in pig thyroid slices by measuring phosphorylation of histone H2AX. L-Buthionine-sulfoximine, an agent that depletes cells of glutathione, decreased the threshold to observe H(2)O(2)-induced DNA damage. Moreover, we showed that DNA breaks induced by H(2)O(2) were more slowly repaired than those induced by irradiation. In conclusion, H(2)O(2) causes SSBs and DSBs in thyroid cells. DSBs are produced in amounts comparable with those observed after irradiation but with a slower repair. These data support the hypothesis that the generation of H(2)O(2) in thyroid could also play a role in mutagenesis particularly in the case of antioxidant defense deficiency.
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PMID:Hydrogen peroxide induces DNA single- and double-strand breaks in thyroid cells and is therefore a potential mutagen for this organ. 1950 65

We have investigated the role of reactive oxygen species and thiol-oxidizing agents in the induction of cell death and have shown that adenocarcinoma gastric (AGS) cells respond differently to the oxidative challenge according to the signaling pathways activated. In particular, apoptosis in AGS cells is induced via the mitochondrial pathway upon treatment with thiol-oxidizing agents, such as diamide. Apoptosis is associated with persistent oxidative damage, as evidenced by the increase in carbonylated proteins and the expression/activation of DNA damage-sensitive proteins histone H2A.X and DNA-dependent protein kinase. Resistance to hydrogen peroxide is instead associated with Keap1 oxidation and rapid translocation of Nrf2 into the nucleus. Sensitivity to diamide and resistance to hydrogen peroxide are correlated with GSH redox changes, with diamide severely increasing GSSG, and hydrogen peroxide transiently inducing protein-GSH mixed disulfides. We show that p53 is activated in response to diamide treatment by the oxidative induction of the Trx1/p38(MAPK) signaling pathway. Similar results were obtained with another carcinoma cell line, CaCo2, indicating that these findings are not limited to AGS cells. Our data suggest that thiol-oxidizing agents could be exploited as inducers of apoptosis in tumor histotypes resistant to ROS-producing chemotherapeutics.
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PMID:Redox mechanisms involved in the selective activation of Nrf2-mediated resistance versus p53-dependent apoptosis in adenocarcinoma cells. 1964 29

Apg-2, a mammalian heat-shock protein belonging to the heat-shock protein 110 (Hsp110) family, was previously found to be overexpressed in BaF3-BCR/ABL cells that were treated with hydrogen peroxide (H2O2) through our comparative proteomics study. The expression of Apg-2 in chronic myelogenous leukemia (CML) cells and its role have not been investigated, forming the basis for this study. BaF3-MIGR1 and BaF3-BCR/ABL cell lines stably overexpressing Apg-2 were established and exposed to 50 microM H2O2 for 10 min. Western blot analysis of Apg-2 expression confirmed that H2O2 treatment significantly up-regulated Apg-2 expression. Apg-2 overexpression elevated BaF3-BCR/ABL cell proportions in S and G2/M phase, increased cell proliferation and colony formation in vitro. Moreover, BaF3-MIGR1 and BaF3-BCR/ABL cells were exposed to 50 microM H2O2 in the absence or presence of Apg-2 overexpression and induction of H2AX phosphorylation, the reporters of DNA damage were assessed by Western blot and immunofluorescence. Results showed that exposure to H2O2 induced H2AX phosphorylation in BaF3-MIGR1 cells, but no increase was observed in BaF3-BCR/ABL cells. Together, the data indicate that Apg-2 is overexpressed and overexpression of Apg-2 in BaF3-BCR/ABL cells increases cell proliferation and protects cells from oxidative damage, which may play an important role in CML carcinogenesis and progression.
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PMID:Overexpression of Apg-2 increases cell proliferation and protects from oxidative damage in BaF3-BCR/ABL cells. 2019 34

The aim of the current study was to determine the signaling differences between gamma- and proton beam-irradiations. A549 lung adenocarcinoma cells were irradiated with 2 Gy proton beam or gamma-radiation. Proton beam was found to be more cytotoxic than gamma-radiation. Proton beam-irradiated cells showed phosphorylation of H2AX, ATM, Chk2, and p53. The mechanism of excessive cell killing in proton beam-irradiated cells was found to be upregulation of Bax and downregulation of Bcl-2. The noteworthy finding of this study is the biphasic activation of the sensor proteins, ATM, and DNA-PK and no activation of ATR by proton irradiation.
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PMID:Low energy proton beam induces efficient cell killing in A549 lung adenocarcinoma cells. 2021 May 20

Hydroxycinnamic acid amides of serotonin (HCAAS) [caffeoylserotonin (compound 1), p-coumaroylserotonin (compound 2), and feruloylserotonin (compound 3)] are secondary metabolites produced in plants. The aim of this study was to investigate the cytoprotective effects of HCAAS based on intracellular reactive oxygen radical (ROS) generation, lipid peroxidation, protein carbonylation, and phosphorylation of histone H2AX in H(2)O(2) treated-HepG2 and HaCaT cells. We have shown that HCAAS showed various strong antioxidant activities in hydrogen peroxide treated both cell lines, suggesting that these compounds may play as chemotherapeutic agents for preventing or reducing the oxidative stress-induced diseases.
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PMID:Cytoprotective activities of hydroxycinnamic acid amides of serotonin against oxidative stress-induced damage in HepG2 and HaCaT cells. 2065 90


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