scholarly journals TNFα-Induced Apoptosis Enabled by CCN1/CYR61: Pathways of Reactive Oxygen Species Generation and Cytochrome c Release

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31303 ◽  
Author(s):  
Vladislava Juric ◽  
Chih-Chiun Chen ◽  
Lester F. Lau
Keyword(s):  
Reactive Oxygen Species ◽  
Cytochrome C ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cytochrome C Release ◽  
Induced Apoptosis

scholarly journals Protection of Pancreatic β-Cells by Group VIA Phospholipase A2-Mediated Repair of Mitochondrial Membrane Peroxidation

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3038-3048 ◽  
Author(s):  
Zhengshan Zhao ◽  
Xu Zhang ◽  
Chunying Zhao ◽  
Jinwoo Choi ◽  
Jieyi Shi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cytochrome C ◽  
Phospholipase A2 ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Β Cells ◽  
Cytochrome C Release ◽  
Induced Apoptosis ◽  
Membrane Peroxidation

Mitochondrial production of reactive oxygen species and oxidation of cardiolipin are key events in initiating apoptosis. We reported that group VIA Ca2+-independent phospholipase A2 (iPLA2β) localizes in and protects β-cell mitochondria from oxidative damage during staurosporine-induced apoptosis. Here, we used iPLA2β-null (iPLA2β−/−) mice to investigate the role of iPLA2β in the repair of mitochondrial membranes. We show that islets isolated from iPLA2β−/− mice are more sensitive to staurosporine-induced apoptosis than those from wild-type littermates and that 2 wk of daily ip administration of staurosporine to iPLA2β−/− mice impairs both the animals’ glucose tolerance and glucose-stimulated insulin secretion by their pancreatic islets. Moreover, the iPLA2β inhibitor bromoenol lactone caused mitochondrial membrane peroxidation and cytochrome c release, and these effects were reversed by N-acetyl cysteine. The mitochondrial antioxidant N-t-butyl hydroxylamine blocked staurosporine-induced cytochrome c release and caspase-3 activation in iPLA2β−/− islets. Furthermore, the collapse of mitochondrial membrane potential in INS-1 insulinoma cells caused by high glucose and fatty acid levels was attenuated by overexpressing iPLA2β. Interestingly, iPLA2β was expressed only at low levels in islet β-cells from obesity- and diabetes-prone db/db mice. These findings support the hypothesis that iPLA2β is important in repairing oxidized mitochondrial membrane components (e.g. cardiolipin) and that this prevents cytochrome c release in response to stimuli that otherwise induce apoptosis. The low iPLA2β expression level in db/db mouse β-cells may render them vulnerable to injury by reactive oxygen species.

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.

Contrasting Role of Concentration in Rivaroxaban Induced Toxicity and Oxidative Stress in Isolated Kidney Mitochondria

Drug Research ◽  
2019 ◽  
Vol 69 (10) ◽  
pp. 523-527
Author(s):  
Fatemeh Samiei ◽  
Hanieh Sajjadi ◽  
Akram Jamshidzadeh ◽  
Enayatollah Seydi ◽  
Jalal Pourahmad
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cytochrome C Release ◽  
Rat Kidneys

AbstractRivaroxaban as a small molecule is able to directly and reversibly inhibit the factor Xa. This study was designed to figure out the evaluation effect of rivaroxaban on mitochondria obtained from rat kidneys. We isolated mitochondria from rat kidneys using gradient centrifugation. Then, the toxicity parameters including succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial swelling, mitochondrial membrane potential (MMP) collapse and cytochrome c release were measured in kidneys mitochondria following the exposure to rivaroxaban. The results showed that rivaroxaban (1.4 and 2.8 mM) raised the reactive oxygen species (ROS) generation, swelling in the mitochondria, collapse in the mitochondrial membrane potential (MMP) and cytochrome c release in the mitochondria isolated from kidneys. While, rivaroxaban at a higher concentration of 5.6 mM showed the opposite effect compared to other lower concentrations. The results indicate that rivaroxaban may have antioxidant effects at high concentrations. The results suggest that rivaroxaban (5.6 mM) has protective effects against oxidative stress and mitochondrial toxicity.

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