Abstract 1661: Autophagy induced by cathepsin S inhibition causes early ROS production for oxidative DNA damage and subsequent cell death.

2013 ◽  
Author(s):  
Chien-Chang Huang ◽  
Jang-Yang Chang
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Oxidative Dna Damage ◽  
Cathepsin S ◽  
Ros Production

scholarly journals Serine-70 phosphorylated Bcl-2 prevents oxidative stress-induced DNA damage by modulating the mitochondrial redox metabolism

2020 ◽  
Vol 48 (22) ◽  
pp. 12727-12745 ◽  
Author(s):  
Stephen Jun Fei Chong ◽  
Kartini Iskandar ◽  
Jolin Xiao Hui Lai ◽  
Jianhua Qu ◽  
Deepika Raman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Lines ◽  
Ros Production ◽  
Primary Cells ◽  
Mitochondrial Complex ◽  
Drug Induced ◽  
Complex Iv ◽  
Redox Sensor

Abstract Bcl-2 phosphorylation at serine-70 (S70pBcl2) confers resistance against drug-induced apoptosis. Nevertheless, its specific mechanism in driving drug-resistance remains unclear. We present evidence that S70pBcl2 promotes cancer cell survival by acting as a redox sensor and modulator to prevent oxidative stress-induced DNA damage and execution. Increased S70pBcl2 levels are inversely correlated with DNA damage in chronic lymphocytic leukemia (CLL) and lymphoma patient-derived primary cells as well as in reactive oxygen species (ROS)- or chemotherapeutic drug-treated cell lines. Bioinformatic analyses suggest that S70pBcl2 is associated with lower median overall survival in lymphoma patients. Empirically, sustained expression of the redox-sensitive S70pBcl2 prevents oxidative stress-induced DNA damage and cell death by suppressing mitochondrial ROS production. Using cell lines and lymphoma primary cells, we further demonstrate that S70pBcl2 reduces the interaction of Bcl-2 with the mitochondrial complex-IV subunit-5A, thereby reducing mitochondrial complex-IV activity, respiration and ROS production. Notably, targeting S70pBcl2 with the phosphatase activator, FTY720, is accompanied by an enhanced drug-induced DNA damage and cell death in CLL primary cells. Collectively, we provide a novel facet of the anti-apoptotic Bcl-2 by demonstrating that its phosphorylation at serine-70 functions as a redox sensor to prevent drug-induced oxidative stress-mediated DNA damage and execution with potential therapeutic implications.

DNA repair BER pathway inhibition increases cell death caused by oxidative DNA damage in Trypanosoma cruzi

2011 ◽  
Vol 112 (8) ◽  
pp. 2189-2199 ◽  
Author(s):  
G. Cabrera ◽  
C. Barría ◽  
C. Fernández ◽  
S. Sepúlveda ◽  
L. Valenzuela ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Dna Repair ◽  
Trypanosoma Cruzi ◽  
Oxidative Dna Damage ◽  
Pathway Inhibition

scholarly journals OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Zhong-Jie Liu ◽  
Wei Zhao ◽  
Qing-Guo Zhang ◽  
Le Li ◽  
Lu-Ying Lai ◽  
...  
Keyword(s):  
Dna Damage ◽  
High Glucose ◽  
Oxidative Dna Damage ◽  
Functional Expression ◽  
Culture Conditions ◽  
Control Culture ◽  
Ros Production ◽  
Dna Oxidative Damage ◽  
Repair Enzymes ◽  
Polymerase Chain

Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use.

scholarly journals Rigosertib-Activated JNK1/2 Eliminate Tumor Cells through p66Shc Activation

Biology ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 99
Author(s):  
Julia K. Günther ◽  
Aleksandar Nikolajevic ◽  
Susanne Ebner ◽  
Jakob Troppmair ◽  
Sana Khalid
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Growth ◽  
Tumor Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Tumor Cell Growth ◽  
Common Pathway ◽  
Growth And Survival

Rigosertib, via reactive oxygen species (ROS), stimulates cJun N-terminal kinases 1/2 (JNK1/2), which inactivate RAS/RAF signaling and thereby inhibit growth and survival of tumor cells. JNK1/2 are not only regulated by ROS—they in turn can also control ROS production. The prooxidant and cell death function of p66Shc requires phosphorylation by JNK1/2. Here, we provide evidence that establishes p66Shc, an oxidoreductase, as a JNK1/2 effector downstream of Rigosertib-induced ROS production, DNA damage, and cell death. This may provide a common pathway for suppression of tumor cell growth by Rigosertib.

Mechanism for manganese enhancement of dopamine-induced oxidative DNA damage and neuronal cell death

2006 ◽  
Vol 41 (5) ◽  
pp. 748-756 ◽  
Author(s):  
Shinji Oikawa ◽  
Iwao Hirosawa ◽  
Saeko Tada-Oikawa ◽  
Ayako Furukawa ◽  
Kaoru Nishiura ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Oxidative Dna Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Tissue Microenvironments within Functional Cortical Subdivisions Adjacent to Focal Stroke

2003 ◽  
Vol 23 (9) ◽  
pp. 997-1009 ◽  
Author(s):  
Diana Katsman ◽  
Jian Zheng ◽  
Kateri Spinelli ◽  
S. Thomas Carmichael
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Somatosensory Cortex ◽  
Oxidative Dna Damage ◽  
Apoptotic Cell ◽  
Reactive Gliosis ◽  
Ischemic Damage ◽  
Infarct Core

Stroke produces a region of complete cell death and areas of partial damage, injury, and gliosis. The spatial relationship of these regions of damage to the infarct core and within spared neuronal circuits has not been identified. A model of cortical stroke was developed within functional subsets of the somatosensory cortex. Infarct size, regions of apoptosis, oxidative DNA damage, heat shock protein induction, and subtypes of reactive gliosis were precisely mapped with the somatosensory body map, quantified, and interrelated. Three tissue microenvironments were recognized: zones of partial ischemic damage, heat shock protein induction, and distributed gliosis. These three zones involved progressively more distant cortical regions, each larger than the infarct core. The zone of partial ischemic damage represents an overlap region of apoptotic cell death, oxidative DNA damage, loss of synaptic connections, and local reactive gliosis. The zone of distributed gliosis occupies distinct functional areas of the somatosensory cortex. The tissue reorganization induced by stroke is much larger than the stroke site itself. Adjacent tissue microenvironments are sites of distinct reactive cellular signaling and may serve as a link between the processes of acute cell death and delayed neuronal plasticity after focal stroke.

scholarly journals Chloro-benzoquinones cause oxidative DNA damage through iron-mediated ROS production in Escherichia coli

Chemosphere ◽  
2015 ◽  
Vol 135 ◽  
pp. 379-386 ◽  
Author(s):  
Zhilan Chen ◽  
Qiaohong Zhou ◽  
Dandan Zou ◽  
Yun Tian ◽  
Biyun Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Ros Production

scholarly journals Cerium Oxide Nanoparticles Induced Toxicity in Human Lung Cells: Role of ROS Mediated DNA Damage and Apoptosis

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sandeep Mittal ◽  
Alok K. Pandey
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cerium Oxide ◽  
Oxidative Dna Damage ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
A549 Cells ◽  
Cerium Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Human Lung Cells

Cerium oxide nanoparticles (CeO2NPs) have promising industrial and biomedical applications. In spite of their applications, the toxicity of these NPs in biological/physiological environment is a major concern. Present study aimed to understand the molecular mechanism underlying the toxicity of CeO2NPs on lung adenocarcinoma (A549) cells. After internalization, CeO2NPs caused significant cytotoxicity and morphological changes in A549 cells. Further, the cell death was found to be apoptotic as shown by loss in mitochondrial membrane potential and increase in annexin-V positive cells and confirmed by immunoblot analysis of BAX, BCl-2, Cyt C, AIF, caspase-3, and caspase-9. A significant increase in oxidative DNA damage was found which was confirmed by phosphorylation of p53 gene and presence of cleaved poly ADP ribose polymerase (PARP). This damage could be attributed to increased production of reactive oxygen species (ROS) with concomitant decrease in antioxidant “glutathione (GSH)” level. DNA damage and cell death were attenuated by the application of ROS and apoptosis inhibitors N-acetyl-L- cysteine (NAC) and Z-DEVD-fmk, respectively. Our study concludes that ROS mediated DNA damage and cell cycle arrest play a major role in CeO2NPs induced apoptotic cell death in A549 cells. Apart from beneficial applications, these NPs also impart potential harmful effects which should be properly evaluated prior to their use.

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