scholarly journals Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Lei Sun ◽  
Tongsheng Chen ◽  
Xiaoping Wang ◽  
Yun Chen ◽  
Xunbin Wei
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Temporal Dynamics ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Induced Apoptosis

Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after bufalin treatment in living cells expressed with green fluorescent protein Bax. Treatment with the antioxidantN-acetyl-cysteine (NAC), a ROS scavenger, inhibited ROS generation and Bax translocation and led to a significant protection against bufalin-induced apoptosis. Our results also revealed that bufalin induced a prominent increase of caspase-3 activation blocked potently by NAC. Taken together, bufalin induced ROS-mediated Bax translocation, mitochondrial permeability transition and caspase-3 activation, implying that bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a-1 cells.

Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages

2001 ◽  
Vol 280 (1) ◽  
pp. L10-L17 ◽  
Author(s):  
Han-Ming Shen ◽  
Zhuo Zhang ◽  
Qi-Feng Zhang ◽  
Choon-Nam Ong
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Alveolar Macrophages ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Parp Cleavage ◽  
Oxygen Species ◽  
Caspase Activation ◽  
Caspase 9 ◽  
Induced Apoptosis

Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.

z-VAD-fmk augmentation of TNFα-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2970-2972 ◽  
Author(s):  
Andrew S. Cowburn ◽  
Jessica F. White ◽  
John Deighton ◽  
Sarah R. Walmsley ◽  
Edwin R. Chilvers
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Broad Spectrum ◽  
Reactive Oxygen ◽  
Cell Types ◽  
Ros Generation ◽  
Neutrophil Apoptosis ◽  
Oxygen Species ◽  
Caspase Inhibitor ◽  
Induced Apoptosis

Abstract In most cell types constitutive and ligand-induced apoptosis is a caspase-dependent process. In neutrophils, however, the broad-spectrum caspase inhibitor z-VAD-fmk enhances tumor necrosis factor-α (TNFα)-induced cell death, and this has been interpreted as evidence for caspase-dependent and -independent cell death pathways. Our aim was to determine the specificity of the effect of z-VAD-fmk in neutrophils and define the potential mechanism of action. While confirming that z-VAD-fmk (> 100 μM) enhances TNFα-induced neutrophil apoptosis, lower concentrations (1-30 μM) completely blocked TNFα-stimulated apoptosis. Boc-D-fmk, a similar broad-spectrum caspase inhibitor, and z-IETD-fmk, a selective caspase-8 inhibitor, caused a concentration-dependent inhibition of only TNFα-stimulated apoptosis. Moreover, the caspase-9 inhibitor, Ac-LEHD-cmk, had no effect on TNFα-induced apoptosis, and z-VAD-fmk and Boc-D-fmk inhibited TNFα-stimulated reactive oxygen species (ROS) generation. These data suggest that TNFα-induced apoptosis in neutrophils is fully caspase dependent and uses a mitochondrial-independent pathway and that the proapoptotic effects of z-VAD-fmk are compound specific and ROS independent.

scholarly journals Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Yasuhiro Kosuge ◽  
Hiroshi Nango ◽  
Hiroki Kasai ◽  
Takuya Yanagi ◽  
Takayuki Mawatari ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Prostaglandin E2 ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Intracellular Ros

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease characterized by progressive degeneration of motor neurons in the central nervous system. Prostaglandin E2 (PGE2) plays a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. We have shown previously that PGE2 directly induces neuronal death through activation of the E-prostanoid (EP) 2 receptor in differentiated NSC-34 cells, a motor neuron-like cell line. In the present study, to clarify the mechanisms underlying PGE2-induced neurotoxicity, we focused on generation of intracellular reactive oxygen species (ROS) and examined the effects of N-acetylcysteine (NAC), a cell-permeable antioxidant, on PGE2-induced cell death in differentiated NSC-34 cells. Dichlorofluorescein (DCF) fluorescence analysis of PGE2-treated cells showed that intracellular ROS levels increased markedly with time, and that this effect was antagonized by a selective EP2 antagonist (PF-04418948) but not a selective EP3 antagonist (L-798,106). Although an EP2-selective agonist, butaprost, mimicked the effect of PGE2, an EP1/EP3 agonist, sulprostone, transiently but significantly decreased the level of intracellular ROS in these cells. MTT reduction assay and lactate dehydrogenase release assay revealed that PGE2- and butaprost-induced cell death were each suppressed by pretreatment with NAC in a concentration-dependent manner. Western blot analysis revealed that the active form of caspase-3 was markedly increased in the PGE2- and butaprost-treated cells. These increases in caspase-3 protein expression were suppressed by pretreatment with NAC. Moreover, dibutyryl-cAMP treatment of differentiated NSC-34 cells caused intracellular ROS generation and cell death. Our data reveal the existence of a PGE2-EP2 signaling-dependent intracellular ROS generation pathway, with subsequent activation of the caspase-3 cascade, in differentiated NSC-34 cells, suggesting that PGE2 is likely a key molecule linking inflammation to oxidative stress in motor neuron-like NSC-34 cells.

scholarly journals AY4, an agonistic anti-death receptor 4 MAB, induces apoptotic cell death in anaplastic thyroid cancer cells via downregulation of Bcl-xL with reactive oxygen species generation

2013 ◽  
Vol 20 (3) ◽  
pp. 283-291 ◽  
Author(s):  
Bok-Soon Lee ◽  
Hyun-Young Cha ◽  
Yoo Seob Shin ◽  
Yong-Sung Kim ◽  
Chul-Ho Kim
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cancer Cells ◽  
Death Receptor ◽  
Reactive Oxygen ◽  
Expression Level ◽  
Ros Generation ◽  
Oxygen Species ◽  
Induced Apoptosis ◽  
Death Receptor 4

Anaplastic thyroid carcinoma (ATC) is an aggressive human tumor with a median survival of 6 months. We previously developed an agonistic anti-death receptor 4 MAB, AY4, and demonstrated the antitumor effects of AY4 in head and neck cancer cells. Presently, we show that ATC cells are sensitive to AY4 and that the sensitivity correlates with the reduced expression level of Bcl-xL and reactive oxygen species (ROS) generation. AY4 induced death of C-643, U-HTH 7, HTH83, and SW1736 cells. To elucidate the role of ROS generation in AY4-induced apoptosis of ATC cells, U-HTH 7 and SW1736 cells were pretreated with an antioxidant (N-acetyl cysteine, NAC) followed by AY4 treatment. The cell death was blocked by NAC. AY4-induced cell death was accompanied by the downregulation of the anti-apoptotic protein, Bcl-xL (BCL2L1). To examine the link between the apoptotic response and Bcl-xL protein expression, U-HTH 7 cells were transfected with Bcl-xL plasmid. The consequence of the overexpression of Bcl-xL appeared to decrease AY4-mediated cell death by blocking ROS generation in U-HTH 7 cells. By contrast, Bcl-xL knockdown using small interfering RNA of Bcl-xL enhanced AY4 sensitivity in HTH83 and C-643 cells and rendered the cells sensitive to AY4-induced cell death. The results support the conclusion that the expression level of Bcl-xL is important in the AY4-induced apoptosis of ATC cells through ROS generation. AY4 may be a promising tool for ATC therapy.

scholarly journals Reactive Oxygen Species in Host Plant Are Required for an Early Defense Response against Attack of Stagonospora nodorum Berk. Necrotrophic Effectors SnTox

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1586
Author(s):  
Svetlana Veselova ◽  
Tatyana Nuzhnaya ◽  
Guzel Burkhanova ◽  
Sergey Rumyantsev ◽  
Igor Maksimov
Keyword(s):  
Reactive Oxygen Species ◽  
Early Stage ◽  
Reactive Oxygen ◽  
Triticum Aestivum L ◽  
Redox Status ◽  
Stagonospora Nodorum ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Necrotrophic Effectors

Reactive oxygen species (ROS) play a central role in plant immune responses. The most important virulence factors of the Stagonospora nodorum Berk. are multiple fungal necrotrophic effectors (NEs) (SnTox) that affect the redox-status and cause necrosis and/or chlorosis in wheat lines possessing dominant susceptibility genes (Snn). However, the effect of NEs on ROS generation at the early stages of infection has not been studied. We studied the early stage of infection of various wheat genotypes with S nodorum isolates -Sn4VD, SnB, and Sn9MN, carrying a different set of NE genes. Our results indicate that all three NEs of SnToxA, SnTox1, SnTox3 significantly contributed to cause disease, and the virulence of the isolates depended on their differential expression in plants (Triticum aestivum L.). The Tsn1–SnToxA, Snn1–SnTox1and Snn3–SnTox3 interactions played an important role in inhibition ROS production at the initial stage of infection. The Snn3–SnTox3 inhibited ROS production in wheat by affecting NADPH-oxidases, peroxidases, superoxide dismutase and catalase. The Tsn1–SnToxA inhibited ROS production in wheat by affecting peroxidases and catalase. The Snn1–SnTox1 inhibited the production of ROS in wheat by mainly affecting a peroxidase. Collectively, these results show that the inverse gene-for gene interactions between effector of pathogen and product of host sensitivity gene suppress the host’s own PAMP-triggered immunity pathway, resulting in NE-triggered susceptibility (NETS). These results are fundamentally changing our understanding of the development of this economical important wheat disease.

scholarly journals CBIO-07. CELL DEATH INDUCED BY AN OSCILLATING MAGNETIC FIELD IN PATIENT DERIVED GLIOBLASTOMA CELLS IS MEDIATED BY REACTIVE OXYGEN SPECIES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii17-ii17
Author(s):  
Shashank Hambarde ◽  
Martyn Sharpe ◽  
David Baskin ◽  
Santosh Helekar
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cell Viability ◽  
Cortical Neurons ◽  
Reactive Oxygen ◽  
Great Promise ◽  
Antioxidant Vitamin ◽  
Ros Generation ◽  
Oxygen Species ◽  
Novel Therapy

Abstract Noninvasive cancer therapy with minimal side effects would be ideal for improving patient outcome in the clinic. We have developed a novel therapy using strong rotating magnets mounted on a helmet. They generate oscillating magnetic fields (OMF) that penetrate through the skull and cover the entire brain. We have demonstrated that OMF can effectively kill patient derived glioblastoma (GBM) cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes (NHA). Exposure of GBM cells to OMF reduced the cell viability by 33% in comparison to sham-treated cells (p< 0.001), while not affecting NHA cell viability. Time lapse video-microscopy for 16 h after OMF exposure showed a marked elevation of mitochondrial reactive oxygen species (ROS), and rapid apoptosis of GBM cells due to activation of caspase 3. Addition of a potent antioxidant vitamin E analog Trolox effectively blocked OMF-induced GBM cell death. Furthermore, OMF significantly potentiated the cytotoxic effect of the pro-oxidant Benzylamine. The results of our studies demonstrate that OMF-induced cell death is mediated by ROS generation. These results demonstrate a potent oncolytic effect on GBM cells that is novel and unrelated to any previously described therapy, including a very different mechanism of action and different technology compared to Optune therapy. The effect is very powerful, and unlike Optune, can be seen within hours after initiation of treatment. We believe that this technology holds great promise for new, effective and nontoxic treatment of glioblastoma.

Abstract 19967: Differential Roles of the NADPH-Oxidase 1 and 2 in Platelet Activation and Thrombosis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Michael K Delaney ◽  
Kyungho Kim ◽  
Brian Estevez ◽  
Aleksandra Stojanovic-Terpo ◽  
Bo Shen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Platelet Activation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
General Role ◽  
Glycoprotein Vi ◽  
Activation Pathways

Objective: Reactive oxygen species (ROS) generated from activated platelets is known to regulate platelet activation. However, it remains unclear whether and how different isoforms of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases (NOXs) play roles in different platelet activation pathways. Here we investigated the role of NOX1 and NOX2 in different platelet activation pathways using NOX1 and NOX2 knockout mice. Approach and Results: NOX1-/- platelets showed selective defects in G protein coupled receptor (GPCR)-mediated platelet activation induced by thrombin, protease-activated receptor 4 agonist peptide (PAR4AP) and thromboxane A2 analog U46619, but was not affected in platelet activation induced by collagen-related peptide (CRP), a glycoprotein VI (GPVI) agonist. In contrast, NOX2-/- platelets showed potent inhibition of CRP-induced platelet activation, and also showed partial inhibition of thrombin-induced platelet aggregation and secretion. Consistently, production of reactive oxygen species (ROS) was inhibited in NOX1-/- platelets stimulated with thrombin, but not CRP, whereas NOX2-/- platelets showed reduced ROS generation induced by CRP or thrombin. Interestingly, laser-induced arterial thrombosis was impaired in NOX2-/- mice, and in thrombocytopenic mice transfused with NOX2-/- platelets, suggesting an important role for NOX2-dependent platelet ROS production in the laser-induced injury model of thrombosis. Conclusions: NOX1 and NOX2 play differential roles in different platelet activation pathways: NOX1 mediates GPCR-mediated ROS production and platelet activation, whereas NOX2 plays a general role in GPVI- and GPCR-induced ROS production and platelet activation in vitro , and in laser-induced thrombosis in vivo .

Hypoxia-induced reactive oxygen species formation in skeletal muscle

2007 ◽  
Vol 102 (6) ◽  
pp. 2379-2388 ◽  
Author(s):  
Thomas L. Clanton
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Cell Function ◽  
Contractile Activity ◽  
Reactive Oxygen ◽  
Hypoxic Exposure ◽  
Ros Production ◽  
Oxygen Species

The existence of hypoxia-induced reactive oxygen species (ROS) production remains controversial. However, numerous observations with a variety of methods and in many cells and tissue types are supportive of this idea. Skeletal muscle appears to behave much like heart in that in the early stages of hypoxia there is a transient elevation in ROS, whereas in chronic exposure to very severe hypoxia there is evidence of ongoing oxidative stress. Important remaining questions that are addressed in this review include the following. Are there levels of Po2 in skeletal muscle, typical of physiological or mildly pathophysiological conditions, that are low enough to induce significant ROS production? Does the ROS associated with muscle contractile activity reflect imbalances in oxygen uptake and demand that drive the cell to a more reduced state? What are the possible molecular mechanisms by which ROS may be elevated in hypoxic skeletal muscle? Is the production of ROS in hypoxia of physiological significance, both with respect to cell signaling pathways promoting cell function and with respect to damaging effects of long-term exposure? Discussion of these and other topics leads to general conclusions that hypoxia-induced ROS may be a normal physiological response to imbalance in oxygen supply and demand or environmental stress and may play a yet undefined role in normal response mechanisms to these stimuli. However, in chronic and extreme hypoxic exposure, muscles may fail to maintain a normal redox homeostasis, resulting in cell injury or dysfunction.

scholarly journals Nitric Oxide Enhances Cytotoxicity of Lead by Modulating the Generation of Reactive Oxygen Species and Is Involved in the Regulation of Pb2+ and Ca2+ Fluxes in Tobacco BY-2 Cells

Plants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 403 ◽  
Author(s):  
Jiaye Wu ◽  
Yue Zhang ◽  
Ruizhi Hao ◽  
Yuan Cao ◽  
Xiaoyi Shan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Heavy Metal ◽  
Cell Death ◽  
Calcium Homeostasis ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Plant Responses ◽  
Oxygen Species ◽  
In Cells

Lead is a heavy metal known to be toxic to both animals and plants. Nitric oxide (NO) was reported to participate in plant responses to different heavy metal stresses. In this study, we analyzed the function of exogenous and endogenous NO in Pb-induced toxicity in tobacco BY-2 cells, focusing on the role of NO in the generation of reactive oxygen species (ROS) as well as Pb2+ and Ca2+ fluxes using non-invasive micro-test technology (NMT). Pb treatment induced BY-2 cell death and rapid NO and ROS generation, while NO burst occurred earlier than ROS accumulation. The elimination of NO by 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) resulted in a decrease of ROS, and the supplementation of NO by sodium nitroprusside (SNP) caused an increased accumulation of ROS. Furthermore, the addition of exogenous NO stimulated Pb2+ influx, thus promoting Pb uptake in cells and aggravating Pb-induced toxicity in cells, whereas the removal of endogenous NO produced the opposite effect. Moreover, we also found that both exogenous and endogenous NO enhanced Pb-induced Ca2+ effluxes and calcium homeostasis disorder. These results suggest that exogenous and endogenous NO played a critical regulatory role in BY-2 cell death induced by Pb stress by promoting Pb2+ influx and accumulation and disturbing calcium homeostasis.

The Requirement of Reactive Oxygen Species Generation in the Apoptosis of Leukemia Cells Induced by 2-Methoxyestradiol.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4370-4370
Author(s):  
Guo Kunyuan ◽  
Miaorong She ◽  
Haiyan Hu ◽  
Xinqing Niu ◽  
Sanfang Tu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Leukemia Cell ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Induced Apoptosis

Abstract 2-Methoxyestradiol (2-ME) is a new anticancer agent currently under investigation for treatment of leukemia. We evaluated the effects of 2-ME-induced apoptosis in two myeloid leukemia cell lines (U937 and HL-60) in association with reactive oxygen species (ROS) generation. We found that 2-ME resulted in viability decrease in a dose-dependent manner, generated ROS: nitric oxide and superoxide anions, and mitochondria damage. 2-ME-induced apoptosis correlated with increase in ROS. Quenching of ROS with N-acetyl-L-cysteine protected leukemia cells from the cytotoxicity of 2-ME and prevented apoptosis induction by 2-ME. Furthermore, addition of manumycin, a farnesyltransferase inhibitor, demonstrated by our previous studies that induced apoptosis of leukemic cells and induced ROS, significantly enhanced the apoptosis-induced by 2-ME. In conclusion, cellular ROS generation play an important role in the cytotoxic effect of 2-ME. It is possible to use ROS-generation agents such as manumycin to enhance the antileukemic effect. Such a combination strategy need the further in vivo justify and may have potential clinical application.

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