TNFα and reactive oxygen species in necrotic cell death

Cell Research ◽  
2008 ◽  
Vol 18 (3) ◽  
pp. 343-349 ◽  
Author(s):  
Michael J Morgan ◽  
You-Sun Kim ◽  
Zheng-gang Liu
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Necrotic Cell Death ◽  
Oxygen Species ◽  
Necrotic Cell

scholarly journals HYD1-induced increase in reactive oxygen species leads to autophagy and necrotic cell death in multiple myeloma cells

2009 ◽  
Vol 8 (8) ◽  
pp. 2441-2451 ◽  
Author(s):  
Rajesh R. Nair ◽  
Michael F. Emmons ◽  
Anne E. Cress ◽  
Raul F. Argilagos ◽  
Kit Lam ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Multiple Myeloma ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Necrotic Cell Death ◽  
Oxygen Species ◽  
Necrotic Cell ◽  
Myeloma Cells

Regulation of Fas (CD95)-induced apoptotic and necrotic cell death by reactive oxygen species in macrophages

2005 ◽  
Vol 203 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Djordje Medan ◽  
Liying Wang ◽  
David Toledo ◽  
Bin Lu ◽  
Christian Stehlik ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Necrotic Cell Death ◽  
Oxygen Species ◽  
Necrotic Cell

scholarly journals Mycobacterium tuberculosis Exploits Focal Adhesion Kinase to Induce Necrotic Cell Death and Inhibit Reactive Oxygen Species Production

2021 ◽  
Vol 12 ◽  
Author(s):  
Afrakoma Afriyie-Asante ◽  
Ankita Dabla ◽  
Amy Dagenais ◽  
Stefania Berton ◽  
Robin Smyth ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Reactive Oxygen ◽  
Necrotic Cell Death ◽  
Ros Production ◽  
Oxygen Species ◽  
Necrotic Cell

Tuberculosis is a deadly, contagious respiratory disease that is caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb). Mtb is adept at manipulating and evading host immunity by hijacking alveolar macrophages, the first line of defense against inhaled pathogens, by regulating the mode and timing of host cell death. It is established that Mtb infection actively blocks apoptosis and instead induces necrotic-like modes of cell death to promote disease progression. This survival strategy shields the bacteria from destruction by the immune system and antibiotics while allowing for the spread of bacteria at opportunistic times. As such, it is critical to understand how Mtb interacts with host macrophages to manipulate the mode of cell death. Herein, we demonstrate that Mtb infection triggers a time-dependent reduction in the expression of focal adhesion kinase (FAK) in human macrophages. Using pharmacological perturbations, we show that inhibition of FAK (FAKi) triggers an increase in a necrotic form of cell death during Mtb infection. In contrast, genetic overexpression of FAK (FAK+) completely blocked macrophage cell death during Mtb infection. Using specific inhibitors of necrotic cell death, we show that FAK-mediated cell death during Mtb infection occurs in a RIPK1-depedent, and to a lesser extent, RIPK3-MLKL-dependent mechanism. Consistent with these findings, FAKi results in uncontrolled replication of Mtb, whereas FAK+ reduces the intracellular survival of Mtb in macrophages. In addition, we demonstrate that enhanced control of intracellular Mtb replication by FAK+ macrophages is a result of increased production of antibacterial reactive oxygen species (ROS) as inhibitors of ROS production restored Mtb burden in FAK+ macrophages to same levels as in wild-type cells. Collectively, our data establishes FAK as an important host protective response during Mtb infection to block necrotic cell death and induce ROS production, which are required to restrict the survival of Mtb.

scholarly journals Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Teru Kamogashira ◽  
Chisato Fujimoto ◽  
Tatsuya Yamasoba
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Hearing Loss ◽  
Reactive Oxygen ◽  
Necrotic Cell Death ◽  
Ros Production ◽  
Oxygen Species ◽  
Necrotic Cell ◽  
Cell Death Pathways ◽  
Age Related

Reactive oxygen species (ROS) production is involved in several apoptotic and necrotic cell death pathways in auditory tissues. These pathways are the major causes of most types of sensorineural hearing loss, including age-related hearing loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise-induced hearing loss. ROS production can be triggered by dysfunctional mitochondrial oxidative phosphorylation and increases or decreases in ROS-related enzymes. Although apoptotic cell death pathways are mostly activated by ROS production, there are other pathways involved in hearing loss that do not depend on ROS production. Further studies of other pathways, such as endoplasmic reticulum stress and necrotic cell death, are required.

Reactive Oxygen Species Regulate Spontaneous and Fas-Mediated Apoptosis in SBDS-Deficient Cells.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2036-2036
Author(s):  
Chhaya Ambekar ◽  
Bikul Das ◽  
Herman Yeger ◽  
Yigal Dror
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cell Growth ◽  
Cell Viability ◽  
Cell Survival ◽  
Annexin V ◽  
Necrotic Cell Death ◽  
Oxygen Species ◽  
Necrotic Cell

Abstract Background and hypotheses: Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure, pancreatic insufficiency, and a marked propensity for myelodysplastic syndrome and leukemia. Approximately 90% of the patients have mutations in the SBDS gene, but the function of the gene is unknown. We previously showed that marrow cells from SDS patients and SBDS-deficient HeLa Cells are characterized by accelerated apoptosis, overexpression of Fas and hypersensitive to Fas stimulation. Involvement of reactive oxygen species (ROS; oxidative stress) have been shown to be related to Fas hypersensitivity and overexpression in a variety of cell types. Therefore, we hypothesized that functional deficiency in SBDS in cells that express Fas could lead to impaired ROS generation and a subsequent increase in spontaneous and Fas-mediated apoptosis and decrease in cell growth. Methods: We used shRNA-mediated SBDS-knockdown HeLa cells as a model. We investigated whether SBDS-deficiency increases ROS levels and if antioxidants can rescue the cell growth and apoptosis phenotype. To measure ROS formation cells were incubated with DCFH-DA and fluorescence measured in Gemini Spectra MAX microplate reader. Staining with annexin V and propidium iodide was done to determine apoptosis and necrotic cell death. MTT assay was used to measure cell viability. Results: ROS levels in SBDS knockdown cells were significantly increased compared to control. Apoptosis analysis by annexin V and propidium iodide showed a marked decrease in cell viability in the SBDS-knockdown cells. NAC treatment decreased ROS levels, enhanced ERK phosphorylation (pERK), improved cell viability, and decreased apoptotic and necrotic cell death. Stimulation of the Fas signaling pathway by CH-11 (activating anti-Fas antibody) and Fas ligand showed increased ROS production in SBDS Knockdown cells. CH-11 treatment showed a marked increase in apoptotic and necrotic cell death after 24 and 48hrs incubation. Cell viability decreased by 40% and 80% after 24 and 48hrs incubation with CH-11. Treatment with NAC lowered ROS levels, enhanced pERK expression, protected the cells from Fas-mediated early apoptosis and improved cell survival. Conclusion: We have demonstrated that stable loss of SBDS results in increased ROS levels, leading to apoptotic and necrotic cell death. Thus, increased baseline and Fas-stimulated ROS could result in increased sensitivity to apoptosis and necrotic cell death. NAC appeared to reverse the ROS-mediated decrease in cell survival and apoptotic cell death. Our data support the novel concept that SBDS may be a homeostatic regulator of oxidative stress

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