Reactive oxygen species mediated tissue damage in high energy proton irradiated mouse brain

Myocardial ischemia-reperfusion (I/R) injury is experienced by individuals suffering from cardiovascular diseases such as coronary heart diseases and subsequently undergoing reperfusion treatments in order to manage the conditions. The occlusion of blood flow to the tissue, termed ischemia, can be especially detrimental to the heart due to its high energy demand. Several cellular alterations have been observed upon the onset of ischemia. The danger created by cardiac ischemia is somewhat paradoxical in that a return of blood to the tissue can result in further damage. Reactive oxygen species (ROS) have been studied intensively to reveal their role in myocardial I/R injury. Under normal conditions, ROS function as a mediator in many cell signaling pathways. However, stressful environments significantly induce the generation of ROS which causes the level to exceed body’s antioxidant defense system. Such altered redox homeostasis is implicated in myocardial I/R injury. Despite the detrimental effects from ROS, low levels of ROS have been shown to exert a protective effect in the ischemic preconditioning. In this review, we will summarize the detrimental role of ROS in myocardial I/R injury, the protective mechanism induced by ROS, and potential treatments for ROS-related myocardial injury.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1452696 ◽

2020 ◽

Vol 2020 ◽

pp. 1-20 ◽

Cited By ~ 21

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.

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Is the reactive oxygen species-dependent-NF-κB activation observed in iron-loaded BALB/c mice a key process preventing growth of Leishmania major progeny and tissue-damage?

Microbes and Infection ◽

10.1016/j.micinf.2006.01.004 ◽

2006 ◽

Vol 8 (6) ◽

pp. 1473-1482 ◽

Cited By ~ 10

Author(s):

Sylvia Bisti ◽

Ketty Soteriadou

Keyword(s):

Reactive Oxygen Species ◽

Tissue Damage ◽

Leishmania Major ◽

Reactive Oxygen ◽

Oxygen Species

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Imaging of reactive oxygen species in focal ischemic mouse brain using a radical trapping tracer [3H]hydromethidine

EJNMMI Research ◽

10.1186/s13550-015-0115-1 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 7

Author(s):

Kohji Abe ◽

Misato Tonomura ◽

Miwa Ito ◽

Nozomi Takai ◽

Natsumi Imamoto ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Mouse Brain ◽

Reactive Oxygen ◽

Oxygen Species ◽

Radical Trapping

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Comparing Early Eukaryotic Integration of Mitochondria and Chloroplasts in the Light of Internal ROS Challenges: Timing is of the Essence

mBio ◽

10.1128/mbio.00955-20 ◽

2020 ◽

Vol 11 (3) ◽

Cited By ~ 1

Author(s):

Dave Speijer ◽

Michael Hammond ◽

Julius Lukeš

Keyword(s):

Reactive Oxygen Species ◽

Driving Forces ◽

Reactive Oxygen ◽

High Energy ◽

Oxygen Species ◽

Mitochondrial Ros ◽

Transport Chain ◽

Evolutionary Trajectories ◽

Ros Formation

ABSTRACT When trying to reconstruct the evolutionary trajectories during early eukaryogenesis, one is struck by clear differences in the developments of two organelles of endosymbiotic origin: the mitochondrion and the chloroplast. From a symbiogenic perspective, eukaryotic development can be interpreted as a process in which many of the defining eukaryotic characteristics arose as a result of mutual adaptions of both prokaryotes (an archaeon and a bacterium) involved. This implies that many steps during the bacterium-to-mitochondrion transition trajectory occurred in an intense period of dramatic and rapid changes. In contrast, the subsequent cyanobacterium-to-chloroplast development in a specific eukaryotic subgroup, leading to the photosynthetic lineages, occurred in a full-fledged eukaryote. The commonalities and differences in the two trajectories shed an interesting light on early, and ongoing, eukaryotic evolutionary driving forces, especially endogenous reactive oxygen species (ROS) formation. Differences between organellar ribosomes, changes to the electron transport chain (ETC) components, and mitochondrial codon reassignments in nonplant mitochondria can be understood when mitochondrial ROS formation, e.g., during high energy consumption in heterotrophs, is taken into account. IMPORTANCE The early eukaryotic evolution was deeply influenced by the acquisition of two endosymbiotic organelles - the mitochondrion and the chloroplast. Here we discuss the possibly important role of reactive oxygen species in these processes.

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Mechanism of the Formation of Electronically Excited Species by Oxidative Metabolic Processes: Role of Reactive Oxygen Species

Biomolecules ◽

10.3390/biom9070258 ◽

2019 ◽

Vol 9 (7) ◽

pp. 258 ◽

Cited By ~ 17

Author(s):

Pavel Pospíšil ◽

Ankush Prasad ◽

Marek Rác

Keyword(s):

Reactive Oxygen Species ◽

Molecular Oxygen ◽

Reactive Oxygen ◽

High Energy ◽

Oxygen Species ◽

Human Beings ◽

Metabolic Processes ◽

Excited Species ◽

Electronically Excited

It is well known that biological systems, such as microorganisms, plants, and animals, including human beings, form spontaneous electronically excited species through oxidative metabolic processes. Though the mechanism responsible for the formation of electronically excited species is still not clearly understood, several lines of evidence suggest that reactive oxygen species (ROS) are involved in the formation of electronically excited species. This review attempts to describe the role of ROS in the formation of electronically excited species during oxidative metabolic processes. Briefly, the oxidation of biomolecules, such as lipids, proteins, and nucleic acids by ROS initiates a cascade of reactions that leads to the formation of triplet excited carbonyls formed by the decomposition of cyclic (1,2-dioxetane) and linear (tetroxide) high-energy intermediates. When chromophores are in proximity to triplet excited carbonyls, the triplet-singlet and triplet-triplet energy transfers from triplet excited carbonyls to chromophores result in the formation of singlet and triplet excited chromophores, respectively. Alternatively, when molecular oxygen is present, the triplet-singlet energy transfer from triplet excited carbonyls to molecular oxygen initiates the formation of singlet oxygen. Understanding the mechanism of the formation of electronically excited species allows us to use electronically excited species as a marker for oxidative metabolic processes in cells.

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Protection by an antioxidant of rotenone-induced neuromotor decline, reactive oxygen species generation and cellular stress in mouse brain

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2012.02.011 ◽

2012 ◽

Vol 101 (3) ◽

pp. 487-492 ◽

Cited By ~ 13

Author(s):

Kodeeswaran Parameshwaran ◽

Michael H. Irwin ◽

Kosta Steliou ◽

Carl A. Pinkert

Keyword(s):

Reactive Oxygen Species ◽

Mouse Brain ◽

Cellular Stress ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species

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Sildenafil Reduces Expression and Release of IL-6 and IL-8 Induced by Reactive Oxygen Species in Systemic Sclerosis Fibroblasts

International Journal of Molecular Sciences ◽

10.3390/ijms21093161 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3161 ◽

Cited By ~ 4

Author(s):

Luigi Di Luigi ◽

Paolo Sgrò ◽

Guglielmo Duranti ◽

Stefania Sabatini ◽

Daniela Caporossi ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Systemic Sclerosis ◽

Tissue Damage ◽

Human Fibroblasts ◽

Reactive Oxygen ◽

Dermal Fibroblasts ◽

Vascular Damage ◽

Oxygen Species ◽

Phosphodiesterase Type 5 Inhibitor

Oxidative stress linked to vascular damage plays an important role in the pathogenesis of systemic sclerosis (SSc). Indeed, vascular damage at nailfold capillaroscopy in patients with Raynaud’s Phenomenon (RP) is a major risk factor for the development of SSc together with the presence of specific autoantiobodies. Here, we investigated the effects of the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil, currently used in the management of RP, in modulating the proinflammatory response of dermal fibroblasts to oxidative stress in vitro. Human fibroblasts isolated from SSc patients and healthy controls were exposed to exogenous reactive oxygen species (ROS) (100 µM H2O2), in the presence or absence of sildenafil (1 µM). Treatment with sildenafil significantly reduced dermal fibroblast gene expression and cellular release of IL-6, known to play a central role in the pathogenesis of tissue damage in SSc and IL-8, directly induced by ROS. This reduction was associated with suppression of STAT3-, ERK-, NF-κB-, and PKB/AKT-dependent pathways. Our findings support the notion that the employment of PDE5i in the management of RP may be explored for its efficacy in modulating the oxidative stress-induced proinflammatory activation of dermal fibroblasts in vivo and may ultimately aid in the prevention of tissue damage caused by SSc.

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Attenuation of Ischemia-Induced Mouse Brain Injury by SAG, a Redox-Inducible Antioxidant Protein

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200106000-00010 ◽

2001 ◽

Vol 21 (6) ◽

pp. 722-733 ◽

Cited By ~ 44

Author(s):

Guo-Yuan Yang ◽

Li Pang ◽

Hai-Liang Ge ◽

Mingjia Tan ◽

Wen Ye ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Brain Injury ◽

Mouse Brain ◽

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Model Systems ◽

Oxygen Species ◽

Antioxidant Protein

Cerebral ischemia resulting from a disruption of blood flow to the brain initiates a cascade of events that causes neuron death and leads to neurologic dysfunction. Reactive oxygen species are thought, at least in part, to mediate this disease process. The authors recently cloned and characterized an antioxidant protein, SAG (sensitive to apoptosis gene), that is redox inducible and protects cells from apoptosis induced by redox agents in a number of in vitro cell model systems. This study reports a neuroprotective role of SAG in ischemia/reperfusion-induced brain injury in an in vivo mouse model. SAG was expressed at a low level in brain tissue and was inducible after middle cerebral artery occlusion with peak expression at 6 to 12 hours. At the cellular level, SAG was mainly expressed in the cytoplasm of neurons and astrocytes, revealed by double immunofluorescence. An injection of recombinant adenoviral vector carrying human SAG into mouse brain produced an overexpression of SAG protein in the injected areas. Transduction of AdCMVSAG (wild-type), but not AdCMVmSAG (mutant), nor the AdCMVlacZ control, protected brain cells from ischemic brain injury, as evidenced by significant reduction of the infarct areas where SAG was highly expressed. The result suggests a rather specific protective role of SAG in the current in vivo model. Mechanistically, SAG overexpression decreased reactive oxygen species production and reduced the number of apoptotic cells in the ischemic areas. Thus, antioxidant SAG appears to protect against reactive oxygen species–induced brain damage in mice. Identification of SAG as a neuroprotective molecule could lead to potential stroke therapies.

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