scholarly journals Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 320 ◽  
Author(s):  
Shuya Kasai ◽  
Sunao Shimizu ◽  
Yota Tatara ◽  
Junsei Mimura ◽  
Ken Itoh
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Physiological Stress ◽  
Reactive Oxygen ◽  
Negative Regulator ◽  
Endurance Capacity ◽  
Oxygen Species ◽  
Antioxidant Genes ◽  
Beneficial Effects ◽  
Quantity Control

Reactive oxygen species (ROS) are byproducts of aerobic respiration and signaling molecules that control various cellular functions. Nrf2 governs the gene expression of endogenous antioxidant synthesis and ROS-eliminating enzymes in response to various electrophilic compounds that inactivate the negative regulator Keap1. Accumulating evidence has shown that mitochondrial ROS (mtROS) activate Nrf2, often mediated by certain protein kinases, and induce the expression of antioxidant genes and genes involved in mitochondrial quality/quantity control. Mild physiological stress, such as caloric restriction and exercise, elicits beneficial effects through a process known as “mitohormesis”. Exercise induces NOX4 expression in the heart, which activates Nrf2 and increases endurance capacity. Mice transiently depleted of SOD2 or overexpressing skeletal muscle-specific UCP1 exhibit Nrf2-mediated antioxidant gene expression and PGC1α-mediated mitochondrial biogenesis. ATF4 activation may induce a transcriptional program that enhances NADPH synthesis in the mitochondria and might cooperate with the Nrf2 antioxidant system. In response to severe oxidative stress, Nrf2 induces Klf9 expression, which represses mtROS-eliminating enzymes to enhance cell death. Nrf2 is inactivated in certain pathological conditions, such as diabetes, but Keap1 down-regulation or mtROS elimination rescues Nrf2 expression and improves the pathology. These reports aid us in understanding the roles of Nrf2 in pathophysiological alterations involving mtROS.

scholarly journals Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Chenglin Han ◽  
Zilong Wang ◽  
Yingkun Xu ◽  
Shuxiao Chen ◽  
Yuqing Han ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Antioxidant Genes ◽  
Beneficial Effects ◽  
Cell Functions ◽  
Incidence And Mortality ◽  
Intracellular Ros ◽  
High Incidence

Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by-product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.

scholarly journals Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function

2021 ◽  
Author(s):  
Jee Hyung Sohn ◽  
Yul Ji ◽  
Chang-Yun Cho ◽  
Hahn Nahmgoong ◽  
Sangsoo Lim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Redox Potentials ◽  
Brown Adipocytes ◽  
Erk Activation ◽  
Brown Adipose ◽  
Erk Inhibition ◽  
Glucose 6 Phosphate Dehydrogenase

Reactive oxygen species (ROS) are associated with various roles of brown adipocytes. Glucose-6-phosphate dehydrogenase (G6PD) controls cellular redox potentials by producing NADPH. Although G6PD upregulates cellular ROS levels in white adipocytes, the roles of G6PD in brown adipocytes remain elusive. Here, we found that G6PD defect in brown adipocytes impaired thermogenic function through excessive cytosolic ROS accumulation. Upon cold exposure, G6PD-deficient mutant (G6PD<sup>mut</sup>) mice exhibited cold intolerance and downregulated thermogenic gene expression in brown adipose tissue (BAT). In addition, G6PD-deficient brown adipocytes had increased cytosolic ROS levels, leading to ERK activation. In BAT of G6PD<sup>mut</sup> mice, administration of antioxidant restored the thermogenic activity by potentiating thermogenic gene expression and relieving ERK activation. Consistently, body temperature and thermogenic execution were rescued by ERK inhibition in cold-exposed G6PD<sup>mut</sup> mice. Taken together, these data suggest that G6PD in brown adipocytes would protect against cytosolic oxidative stress, leading to cold-induced thermogenesis.

scholarly journals Freezing Tolerance of Lolium multiflorum/Festuca arundinacea Introgression Forms is Associated with the High Activity of Antioxidant System and Adjustment of Photosynthetic Activity under Cold Acclimation

2020 ◽  
Vol 21 (16) ◽  
pp. 5899 ◽  
Author(s):  
Adam Augustyniak ◽  
Izabela Pawłowicz ◽  
Katarzyna Lechowicz ◽  
Karolina Izbiańska-Jankowska ◽  
Magdalena Arasimowicz-Jelonek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Cold Acclimation ◽  
Antioxidant System ◽  
Freezing Tolerance ◽  
Photosynthetic Apparatus ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Protein Accumulation ◽  
Oxygen Species

Though winter-hardiness is a complex trait, freezing tolerance was proved to be its main component. Species from temperate regions acquire tolerance to freezing in a process of cold acclimation, which is associated with the exposure of plants to low but non-freezing temperatures. However, mechanisms of cold acclimation in Lolium-Festuca grasses, important for forage production in Europe, have not been fully recognized. Thus, two L. multiflorum/F. arundinacea introgression forms with distinct freezing tolerance were used herein as models in the comprehensive research to dissect these mechanisms in that group of plants. The work was focused on: (i) analysis of cellular membranes’ integrity; (ii) analysis of plant photosynthetic capacity (chlorophyll fluorescence; gas exchange; gene expression, protein accumulation, and activity of selected enzymes of the Calvin cycle); (iii) analysis of plant antioxidant capacity (reactive oxygen species generation; gene expression, protein accumulation, and activity of selected enzymes); and (iv) analysis of Cor14b accumulation, under cold acclimation. The more freezing tolerant introgression form revealed a higher integrity of membranes, an ability to cold acclimate its photosynthetic apparatus and higher water use efficiency after three weeks of cold acclimation, as well as a higher capacity of the antioxidant system and a lower content of reactive oxygen species in low temperature.

scholarly journals Reactive Oxygen Species Are Key Mediators of Demyelination in Canine Distemper Leukoencephalitis but not in Theiler’s Murine Encephalomyelitis

2019 ◽  
Vol 20 (13) ◽  
pp. 3217 ◽  
Author(s):  
Attig ◽  
Spitzbarth ◽  
Kalkuhl ◽  
Deschl ◽  
Puff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxidized Lipids ◽  
Ros Generation ◽  
Spinal Cord Tissue ◽  
Oxygen Species ◽  
Canine Distemper ◽  
Membrane Breakdown ◽  
Expression Microarrays

(1) Background: Canine distemper virus (CDV)-induced demyelinating leukoencephalitis (CDV-DL) in dogs and Theiler’s murine encephalomyelitis (TME) virus (TMEV)-induced demyelinating leukomyelitis (TMEV-DL) are virus-induced demyelinating conditions mimicking Multiple Sclerosis (MS). Reactive oxygen species (ROS) can induce the degradation of lipids and nucleic acids to characteristic metabolites such as oxidized lipids, malondialdehyde, and 8-hydroxyguanosine. The hypothesis of this study is that ROS are key effector molecules in the pathogenesis of myelin membrane breakdown in CDV-DL and TMEV-DL. (2) Methods: ROS metabolites and antioxidative enzymes were assessed using immunofluorescence in cerebellar lesions of naturally CDV-infected dogs and spinal cord tissue of TMEV-infected mice. The transcription of selected genes involved in ROS generation and detoxification was analyzed using gene-expression microarrays in CDV-DL and TMEV-DL. (3) Results: Immunofluorescence revealed increased amounts of oxidized lipids, malondialdehyde, and 8-hydroxyguanosine in CDV-DL while TMEV-infected mice did not reveal marked changes. In contrast, microarray-analysis showed an upregulated gene expression associated with ROS generation in both diseases. (4) Conclusion: In summary, the present study demonstrates a similar upregulation of gene-expression of ROS generation in CDV-DL and TMEV-DL. However, immunofluorescence revealed increased accumulation of ROS metabolites exclusively in CDV-DL. These results suggest differences in the pathogenesis of demyelination in these two animal models.

scholarly journals PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Sergio Rius-Pérez ◽  
Isabel Torres-Cuevas ◽  
Iván Millán ◽  
Ángel L. Ortega ◽  
Salvador Pérez
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Metabolic Syndrome ◽  
Inflammatory Response ◽  
Reactive Oxygen ◽  
High Energy ◽  
Low Grade ◽  
Oxygen Species ◽  
Antioxidant Genes ◽  
Integrative View

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a transcriptional coactivator described as a master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation and reactive oxygen species detoxification. PGC-1α is highly expressed in tissues with high energy demands, and it is clearly associated with the pathogenesis of metabolic syndrome and its principal complications including obesity, type 2 diabetes mellitus, cardiovascular disease, and hepatic steatosis. We herein review the molecular pathways regulated by PGC-1α, which connect oxidative stress and mitochondrial metabolism with inflammatory response and metabolic syndrome. PGC-1α regulates the expression of mitochondrial antioxidant genes, including manganese superoxide dismutase, catalase, peroxiredoxin 3 and 5, uncoupling protein 2, thioredoxin 2, and thioredoxin reductase and thus prevents oxidative injury and mitochondrial dysfunction. Dysregulation of PGC-1α alters redox homeostasis in cells and exacerbates inflammatory response, which is commonly accompanied by metabolic disturbances. During inflammation, low levels of PGC-1α downregulate mitochondrial antioxidant gene expression, induce oxidative stress, and promote nuclear factor kappa B activation. In metabolic syndrome, which is characterized by a chronic low grade of inflammation, PGC-1α dysregulation modifies the metabolic properties of tissues by altering mitochondrial function and promoting reactive oxygen species accumulation. In conclusion, PGC-1α acts as an essential node connecting metabolic regulation, redox control, and inflammatory pathways, and it is an interesting therapeutic target that may have significant benefits for a number of metabolic diseases.

scholarly journals 15-Deoxy-Δ12,14-prostaglandin J2Induces Heme Oxygenase-1 Gene Expression in a Reactive Oxygen Species-dependent Manner in Human Lymphocytes

2004 ◽  
Vol 279 (21) ◽  
pp. 21929-21937 ◽  
Author(s):  
Moisés Álvarez-Maqueda ◽  
Rajaa El Bekay ◽  
Gonzalo Alba ◽  
Javier Monteseirín ◽  
Pedro Chacón ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Heme Oxygenase ◽  
Human Lymphocytes ◽  
Reactive Oxygen ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Oxygen Species
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