scholarly journals Mitochondrial reactive oxygen species drive proinflammatory cytokine production

2011 ◽  
Vol 208 (3) ◽  
pp. 417-420 ◽  
Author(s):  
Edwina Naik ◽  
Vishva M. Dixit
Keyword(s):  
Reactive Oxygen Species ◽  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Reactive Oxygen ◽  
Molecular Pathways ◽  
Oxygen Species ◽  
Proinflammatory Cytokine Production ◽  
Mitochondrial Reactive Oxygen Species

High levels of reactive oxygen species (ROS) are observed in chronic human diseases such as neurodegeneration, Crohn’s disease, and cancer. In addition to the presence of oxidative stress, these diseases are also characterized by deregulated inflammatory responses, including but not limited to proinflammatory cytokine production. New work exploring the mechanisms linking ROS and inflammation find that ROS derived from mitochondria act as signal-transducing molecules that provoke the up-regulation of inflammatory cytokine subsets via distinct molecular pathways.

scholarly journals Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS)

2011 ◽  
Vol 208 (3) ◽  
pp. 519-533 ◽  
Author(s):  
Ariel C. Bulua ◽  
Anna Simon ◽  
Ravikanth Maddipati ◽  
Martin Pelletier ◽  
Heiyoung Park ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Proinflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Reactive Oxygen ◽  
Periodic Syndrome ◽  
Oxygen Species ◽  
Inflammatory Cytokine Production ◽  
Mitochondrial Ros ◽  
In Cells

Reactive oxygen species (ROS) have an established role in inflammation and host defense, as they kill intracellular bacteria and have been shown to activate the NLRP3 inflammasome. Here, we find that ROS generated by mitochondrial respiration are important for normal lipopolysaccharide (LPS)-driven production of several proinflammatory cytokines and for the enhanced responsiveness to LPS seen in cells from patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS), an autoinflammatory disorder caused by missense mutations in the type 1 TNF receptor (TNFR1). We find elevated baseline ROS in both mouse embryonic fibroblasts and human immune cells harboring TRAPS-associated TNFR1 mutations. A variety of antioxidants dampen LPS-induced MAPK phosphorylation and inflammatory cytokine production. However, gp91phox and p22phox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits are dispensable for inflammatory cytokine production, indicating that NADPH oxidases are not the source of proinflammatory ROS. TNFR1 mutant cells exhibit altered mitochondrial function with enhanced oxidative capacity and mitochondrial ROS generation, and pharmacological blockade of mitochondrial ROS efficiently reduces inflammatory cytokine production after LPS stimulation in cells from TRAPS patients and healthy controls. These findings suggest that mitochondrial ROS may be a novel therapeutic target for TRAPS and other inflammatory diseases.

scholarly journals Astaxanthin Prevents Atrophy in Slow Muscle Fibers by Inhibiting Mitochondrial Reactive Oxygen Species via a Mitochondria-Mediated Apoptosis Pathway

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 379
Author(s):  
Luchuanyang Sun ◽  
Nobuyuki Miyaji ◽  
Min Yang ◽  
Edward M. Mills ◽  
Shigeto Taniyama ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Bilayer ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Reactive Oxygen ◽  
H2o2 Production ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Tail Suspension ◽  
Apoptosis Pathway

Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle-atrophy-mediated disturbance of mitochondria, which have a lipid bilayer. Tail suspension was used to establish a muscle-atrophied mouse model. AX diet fed to tail-suspension mice prevented loss of muscle weight, inhibited the decrease of myofiber size, and restrained the increase of hydrogen peroxide (H2O2) production in the soleus muscle. Additionally, AX improved downregulation of mitochondrial respiratory chain complexes I and III in the soleus muscle after tail suspension. Meanwhile, AX promoted mitochondrial biogenesis by upregulating the expressions of adenosine 5′-monophosphate–activated protein kinase (AMPK) α-1, peroxisome proliferator–activated receptor (PPAR)-γ, and creatine kinase in mitochondrial (Ckmt) 2 in the soleus muscle of tail-suspension mice. To confirm the AX phenotype in the soleus muscle, we examined its effects on mitochondria using Sol8 myotubes derived from the soleus muscle. We found that AX was preferentially detected in the mitochondrial fraction; it significantly suppressed mitochondrial reactive oxygen species (ROS) production in Sol8 myotubes. Moreover, AX inhibited the activation of caspase 3 via inhibiting the release of cytochrome c into the cytosol in antimycin A–treated Sol8 myotubes. These results suggested that AX protected the functional stability of mitochondria, alleviated mitochondrial oxidative stress and mitochondria-mediated apoptosis, and thus, prevented muscle atrophy.

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