scholarly journals Specific disintegration of complex II succinate:ubiquinone oxidoreductase links pH changes to oxidative stress for apoptosis induction

2010 ◽  
Vol 18 (2) ◽  
pp. 338-349 ◽  
Author(s):  
A Lemarie ◽  
L Huc ◽  
E Pazarentzos ◽  
A-L Mahul-Mellier ◽  
S Grimm
Keyword(s):  
Oxidative Stress ◽  
Apoptosis Induction ◽  
Complex Ii ◽  
Ph Changes ◽  
Succinate:Ubiquinone Oxidoreductase

Apoptosis Induction by Pseudorabies Virus via Oxidative Stress and Subsequent DNA Damage Signaling

Intervirology ◽  
2019 ◽  
Vol 62 (3-4) ◽  
pp. 116-123 ◽  
Author(s):  
I-Hsiang Lai ◽  
Ching-Dong Chang ◽  
Wen-Ling Shih
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Pseudorabies Virus ◽  
Apoptosis Induction ◽  
Dna Damage Signaling

Oxidative stress-mediated cytotoxicity and apoptosis induction by TiO2 nanofibers in HeLa cells

2012 ◽  
Vol 81 (2) ◽  
pp. 324-333 ◽  
Author(s):  
Kunga Mohan Ramkumar ◽  
Chinnasamy Manjula ◽  
Georgepeter GnanaKumar ◽  
Muzafar A. Kanjwal ◽  
Thillai V. Sekar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hela Cells ◽  
Apoptosis Induction ◽  
Tio2 Nanofibers

scholarly journals BH3-only protein Bik is involved in both apoptosis induction and sensitivity to oxidative stress in multiple myeloma

2010 ◽  
Vol 103 (12) ◽  
pp. 1808-1814 ◽  
Author(s):  
L Bodet ◽  
E Ménoret ◽  
G Descamps ◽  
C Pellat-Deceunynck ◽  
R Bataille ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Myeloma ◽  
Apoptosis Induction

Localization of Histidine Residues Responsible for Heme Axial Ligation in Cytochromeb556of Complex II (Succinate:Ubiquinone Oxidoreductase) inEscherichia coli†

Biochemistry ◽  
1998 ◽  
Vol 37 (12) ◽  
pp. 4148-4159 ◽  
Author(s):  
Cecile Rose T. Vibat ◽  
Gary Cecchini ◽  
Kayako Nakamura ◽  
Kiyoshi Kita ◽  
Robert B. Gennis
Keyword(s):  
Inescherichia Coli ◽  
Complex Ii ◽  
Histidine Residues ◽  
Axial Ligation ◽  
Succinate:Ubiquinone Oxidoreductase

scholarly journals Effect of Ubiquinol on Glaucomatous Neurodegeneration and Oxidative Stress: Studies for Retinal Ganglion Cell Survival and/or Visual Function

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 952
Author(s):  
Genea Edwards ◽  
Yonghoon Lee ◽  
Martha Kim ◽  
Soham Bhanvadia ◽  
Keun-Young Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Visual Function ◽  
Therapeutic Potential ◽  
Control Diet ◽  
Retinal Ganglion ◽  
Complex Ii ◽  
Oxphos Complex ◽  
And Oxidative Stress

Oxidative stress is one of major causal factors in glaucomatous neurodegeneration. Ubiquinol promotes retinal ganglion cell (RGC) survival against glaucomatous insults such as oxidative stress. Here we investigated the effect of ubiquinol on RGC survival and/or visual function in mouse models of glaucoma and oxidative stress. DBA/2J and age-matched DBA/2J-Gpnmb+ (D2-Gpnmb+), which do not develop intraocular pressure elevation, or C57BL/6J mice were fed with ubiquinol (1%) or control diet daily for 5 or 2 months. We assessed RGC survival by Brn3a immunohistochemistry and measured expression levels of active and total BAX, peroxisome proliferator-activated receptor-gamma coactivator 1α, transcription factor A (TFAM) and oxidative phosphorylation (OXPHOS) complex protein. Following induction of oxidative stress by paraquat injection, we also assessed visual function. In glaucomatous retina, ubiquinol supplementation significantly promoted RGC survival, blocked BAX activation and increased TFAM and OXPHOS complex II protein expression. Also, ubiquinol supplementation ameliorated oxidative stress-induced visual dysfunction. These findings indicate that ubiquinol promotes RGC survival by increasing TFAM expression and OXPHOS complex II activity in glaucomatous neurodegeneration, and that ubiquinol enhances RGC survival and preserves visual function against oxidative stress. We propose that ubiquinol has a therapeutic potential for treating oxidative stress-associated glaucomatous neurodegeneration.

Mechanistic view for toxic effects of arsenic on isolated rat kidney and brain mitochondria

Biologia ◽  
2015 ◽  
Vol 70 (5) ◽  
Author(s):  
Shokoufeh Hassani ◽  
Hashem Yaghoubi ◽  
Roya Khosrokhavar ◽  
Iman Jafarian ◽  
Vida Mashayekhi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Outer Membrane ◽  
Brain Mitochondria ◽  
Male Rats ◽  
Arsenic Toxicity ◽  
Cytochrome C Release ◽  
Oxidation Stress ◽  
Complex Ii ◽  
Ros Formation

AbstractArsenic is one of the most important risk factors for human health and exhibits carcinogenicity in human. Emerging lines of research indicate that mitochondria are important target organelles for metals toxicity in living cells. In this study male rats were sacrificed and then kidney and brain mitochondria were isolated using ultracentrifugation method. Then, multi-parametric assays including reactive oxygen species (ROS) formation, complex II and IV activity, outer membrane integrity, ATP level and release of cytochrome c release evaluated to predict the biochemical pathways involved in arsenic toxicity. Our results showed that arsenic (25-200 μM) induced significant ROS formation rise and mitochondrial outer membrane damage in kidney and brain mitochondria, mitochondrial membrane potential collapse and mitochondrial ATP levels. Significant decrease in the complex II and IV activity in brain without any change in kidney mitochondria suggests the inevitable role of oxidative stress in mitochondrial permeability transition-mediated cytochrome c release. Therefore, it is supposed that mitochondrial oxidative stress and uncoupling of oxidative phosphorylation may play key roles in arsenic toxicity towards isolated kidney and brain mitochondria. Also, comparison of present study with previous investigations supposed that liver is more susceptible to arsenic exposure and induction of oxidation stress-like condition than kidney and brain tissues.

Thienopyrimidine derivatives exert their anticancer efficacy via apoptosis induction, oxidative stress and mitotic catastrophe

2017 ◽  
Vol 138 ◽  
pp. 1053-1065 ◽  
Author(s):  
Haneen Amawi ◽  
Chandrabose Karthikeyan ◽  
Rekha Pathak ◽  
Noor Hussein ◽  
Ryann Christman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitotic Catastrophe ◽  
Apoptosis Induction ◽  
Anticancer Efficacy

scholarly journals The Pim Kinase Inhibitor AZD1208 Enhances Topoisomerase-2 Inhibitor Induction of Apoptosis of Acute Myeloid Leukemia Cells with FLT3-ITD through Increased Oxidative Stress

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1268-1268
Author(s):  
Kshama A. Doshi ◽  
Karthika Natarajan ◽  
Feyruz V. Rassool ◽  
Dennis Huszar ◽  
Maria R. Baer
Keyword(s):  
Oxidative Stress ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Caspase 3 ◽  
Kinase Inhibitor ◽  
Apoptosis Induction ◽  
Flt3 Inhibitors ◽  
Topoisomerase 2 ◽  
Induction Of Apoptosis ◽  
Acute Myeloid

The receptor tyrosine kinase fms-like tyrosine kinase-3 (FLT3) is expressed on acute myeloid leukemia (AML) cells in most patients, and is mutated most commonly by internal tandem duplication (ITD), in approximately 30% of patients, resulting in constitutive activation and growth signaling. Initial treatment for AML consists of combination chemotherapy including cytarabine (AraC) and a topoisomerase-2 (TOP-2) inhibitor, most commonly daunorubicin (DNR). Other TOP-2 inhibitors, including mitoxantrone (Mitox) and etoposide (VP-16) are also active in AML. AML patients with FLT3-ITD achieve remission, but have high relapse rates and short disease-free survival. FLT3 inhibitors are in clinical trials, but so far with limited and transient activity. Hence new therapeutic approaches targeting additional signaling molecules are needed. Pim-1 kinase, a pro-survival oncogene, is transcriptionally upregulated downstream of FLT3-ITD and promotes its signaling in a positive feedback loop. We have shown that the Pim kinase inhibitor AZD1208 enhances apoptosis induction of FLT3-ITD cells by FLT3 inhibitors, both in vitro and in vivo. We hypothesized that Pim-1 kinase inhibition might also enhance apoptosis induction by chemotherapy drugs. Ba/F3 cells transfected with FLT3-ITD (Ba/F3-ITD) were treated with DNR, Mitox, VP-16 or AraC at their approximate IC50 concentrations with and without 1µM AZD1208, and viable cells were counted. While growth of Ba/F3-ITD was reduced by DNR, Mitox, VP-16 or AraC, it was abrogated by co-treatment with AZD1208 and DNR, Mitox or VP-16, but not AraC. Ba/F3 cells transfected with wild type (WT) FLT3 (Ba/F3-WT) were less sensitive to this effect. To determine whether the effect on growth was cytostatic or cytotoxic, we studied cell cycle by flow cytometric analysis of propidium iodide (PI) staining. A significant increase in Ba/F3-ITD cells in sub-G1 phase was seen following treatment with AZD1208 and TOP-2 inhibitors, compared to TOP-2 inhibitors alone, consistent with enhanced apoptosis. Significant (P<0.0001) increase in apoptosis in multiple FLT3-ITD cell lines, including transfected Ba/F3-ITD and 32D-ITD cells and human AML cells MV4-11 and MOLM-14, co-treated with AZD1208 and TOP-2 inhibitors was confirmed using Annexin V/PI staining. Minimal or no effect was seen with combination treatment in Ba/F3-WT or 32D-WT cells. Further, treatment of Ba/F3-ITD cells with AZD1208 and TOP-2 inhibitors, in relation to TOP-2 inhibitors alone, accelerated loss of mitochondrial membrane potential (MMP) and increased cytochrome c release, caspase-3 activation and PARP cleavage. Enhanced induction of apoptosis (P<0.001) was also seen in FLT3-ITD AML patient samples co-treated with AZD1208 and TOP-2 inhibitors, in relation to TOP-2 inhibitors alone, but was not seen in FLT3-WT AML patient samples, nor in AML remission bone marrow samples, with the latter observation supporting a favorable therapeutic index. Consistent with the effects on cell growth, co-treatment with AZD1208 did not sensitize Ba/F3-ITD cells to apoptosis induction by AraC, and AZD1208 actually modestly decreased AraC-induced apoptosis in Ba/F3-ITD (P<0.0001) and 32D-ITD (P<0.01) cells. Additionally co-treatment with AZD1208 and AraC decreased AraC-induced loss of MMP, release of cytochrome c and caspase-3 activation in Ba/F3-ITD cells (P<0.001). Mechanistically, when compared to TOP-2 inhibitors alone, co-treatment with AZD1208 and TOP-2 inhibitors increased oxidative stress in Ba/F3-ITD cells, as evidenced by more than two-fold increased generation of reactive oxygen species (ROS). Further, treatment with the ROS scavenger N-acetyl cysteine markedly attenuated the increase in apoptosis produced by AZD1208 and TOP-2 inhibitors, consistent with a causative role of ROS production in apoptosis induction, through increased DNA damage. Finally, consistent with the lack of increase in apoptosis, co-treatment with AZD1208 and AraC did not increase ROS generation. We conclude that Pim kinase inhibition enhances induction of apoptosis of AML cells with FLT3-ITD by TOP-2 inhibitors, but not AraC, through increased oxidative stress. The selective effect in FLT3-ITD cells may be due to high baseline ROS levels and/or Pim-1 kinase overexpression. Our work supports potential clinical applicability of combining a Pim kinase inhibitor with TOP-2 inhibitors, but not AraC, to treat AML with FLT3-ITD. Disclosures Huszar: Astra Zeneca: Employment.

scholarly journals Human adipose-derived stem cells obtained from lipoaspirates are highly susceptible to hydrogen peroxide mediated cytogenotoxicity

2019 ◽  
Vol 1 (1) ◽  
pp. 11-28
Author(s):  
Alencar Kolinski Machado ◽  
Sabrina Guastavino Homrich ◽  
Cíntia Corte Real Rodrigues ◽  
Verônica Farina Azzolin ◽  
Marta Maria Medeiros Frescura Duarte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Safety Profile ◽  
Mortality Rates ◽  
Adipose Derived Stem Cells ◽  
Apoptosis Induction ◽  
Genotoxic Effects ◽  
Dna Comet Assay ◽  
Stress Markers ◽  
Highly Sensitive

There is evidence that H2O2 can induce the proliferation, migration, and regeneration of stem cells, as well as that of adipose-derived stem cells (ASCs). This could be useful to expand the possible uses of ASCs in therapeutic applications.  However, the safety profile of H2O2 use in stem cells is not clear yet. Therefore, the present study evaluated the acute cytotoxic, oxidative and genotoxic effects of different concentrations of H2O2 on ASCs obtained from human lipoaspirates. The ASCs were treated with 1–1000 μM H2O2 for two hours. Cell viability was evaluated by double-strand DNA determination. Apoptosis induction was analyzed measuring active levels of caspases 1, 3 and 8. Biochemical oxidative stress markers were analyzed and genotoxic effects were assessed by DNA comet assay. All H2O2 concentrations increased ASC mortality rates with approximately 100% mortality achieved at ≥ 200 μM. Active caspases 1, 3 and 8, oxidative stress, as well as oxidative damage as assessed by lipid peroxidation increased dose‐dependently. There was also an approximate 50% increase in catalase levels in cells exposed to all H2O2 tested concentrations. H2O2 concentrations of ≥ 10 μM were genotoxic. These results suggest that ASCs are highly sensitive to H2O2 exposition. In addition, DNA damage in the surviving cells may affect their proliferative and differentiation capacity, as well as their safety profile for therapeutic use.

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