scholarly journals TrpML-mediated astrocyte microdomain Ca2+ transients regulate astrocyte–tracheal interactions

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Zhiguo Ma ◽  
Marc R Freeman
Keyword(s):  
Reactive Oxygen Species ◽  
Central Nervous System ◽  
Gas Exchange ◽  
Brain Function ◽  
Ros Production ◽  
Oxygen Species ◽  
Membrane Microdomain ◽  
The Central Nervous System ◽  
Temporally Correlated

Astrocytes exhibit spatially-restricted near-membrane microdomain Ca2+transients in their fine processes. How these transients are generated and regulate brain function in vivo remains unclear. Here we show that Drosophila astrocytes exhibit spontaneous, activity-independent microdomain Ca2+ transients in their fine processes. Astrocyte microdomain Ca2+ transients are mediated by the TRP channel TrpML, stimulated by reactive oxygen species (ROS), and can be enhanced in frequency by the neurotransmitter tyramine via the TyrRII receptor. Interestingly, many astrocyte microdomain Ca2+ transients are closely associated with tracheal elements, which dynamically extend filopodia throughout the central nervous system (CNS) to deliver O2 and regulate gas exchange. Many astrocyte microdomain Ca2+ transients are spatio-temporally correlated with the initiation of tracheal filopodial retraction. Loss of TrpML leads to increased tracheal filopodial numbers, growth, and increased CNS ROS. We propose that local ROS production can activate astrocyte microdomain Ca2+ transients through TrpML, and that a subset of these microdomain transients promotes tracheal filopodial retraction and in turn modulate CNS gas exchange.

scholarly journals TrpML-mediated astrocyte microdomain Ca2+ transients regulate astrocyte-tracheal interactions

2019 ◽  
Author(s):  
Zhiguo Ma ◽  
Marc R. Freeman
Keyword(s):  
Reactive Oxygen Species ◽  
Central Nervous System ◽  
Gas Exchange ◽  
Brain Function ◽  
Ros Production ◽  
Oxygen Species ◽  
Membrane Microdomain ◽  
The Central Nervous System ◽  
Temporally Correlated

AbstractAstrocytes exhibit spatially-restricted near-membrane microdomain Ca2+ transients in their fine processes. How these transients are generated and regulate brain function in vivo remains unclear. Here we show that Drosophila astrocytes exhibit spontaneous, activity-independent microdomain Ca2+ transients in their fine processes. Astrocyte microdomain Ca2+ transients are mediated by the TRP channel TrpML, stimulated by reactive oxygen species (ROS), and can be enhanced in frequency by the neurotransmitter tyramine via the TyrRII receptor. Interestingly, many astrocyte microdomain Ca2+ transients are closely associated with tracheal elements, which dynamically extend filopodia throughout the central nervous system (CNS) to deliver O2 and regulate gas exchange. Many astrocyte microdomain Ca2+ transients are spatio-temporally correlated with the initiation of tracheal filopodial retraction. Loss of TrpML leads to increased tracheal filopodial numbers, growth, and increased CNS ROS. We propose that local ROS production can activate astrocyte microdomain Ca2+ transients through TrpML, and that a subset of these microdomain transients promotes tracheal filopodial retraction and in turn modulate CNS gas exchange.

scholarly journals Loss of the SdhB, but Not the SdhA, Subunit of Complex II Triggers Reactive Oxygen Species-Dependent Hypoxia-Inducible Factor Activation and Tumorigenesis

2007 ◽  
Vol 28 (2) ◽  
pp. 718-731 ◽  
Author(s):  
Robert D. Guzy ◽  
Bhumika Sharma ◽  
Eric Bell ◽  
Navdeep S. Chandel ◽  
Paul T. Schumacker
Keyword(s):  
Reactive Oxygen Species ◽  
Rna Interference ◽  
Growth Rates ◽  
Hypoxia Inducible Factor ◽  
Tumor Formation ◽  
Ros Production ◽  
Oxygen Species ◽  
Complex Ii

ABSTRACT Mitochondrial complex II is a tumor suppressor comprised of four subunits (SdhA, SdhB, SdhC, and SdhD). Mutations in any of these should disrupt complex II enzymatic activity, yet defects in SdhA produce bioenergetic deficiency while defects in SdhB, SdhC, or SdhD induce tumor formation. The mechanisms underlying these differences are not known. We show that the inhibition of distal subunits of complex II, either pharmacologically or via RNA interference of SdhB, increases normoxic reactive oxygen species (ROS) production, increases hypoxia-inducible factor alpha (HIF-α) stabilization in an ROS-dependent manner, and increases growth rates in vitro and in vivo without affecting hypoxia-mediated activation of HIF-α. Proximal pharmacologic inhibition or RNA interference of complex II at SdhA, however, does not increase normoxic ROS production or HIF-α stabilization and results in decreased growth rates in vitro and in vivo. Furthermore, the enhanced growth rates resulting from SdhB suppression are inhibited by the suppression of HIF-1α and/or HIF-2α, indicating that the mechanism of SdhB-induced tumor formation relies upon ROS production and subsequent HIF-α activation. Therefore, differences in ROS production, HIF proliferation, and cell proliferation contribute to the differences in tumor phenotype in cells lacking SdhB as opposed to those lacking SdhA.

scholarly journals The H2S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2966 ◽  
Author(s):  
Milica Lazarević ◽  
Emanuela Mazzon ◽  
Miljana Momčilović ◽  
Maria Basile ◽  
Giuseppe Colletti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Microglial Cells ◽  
Oxygen Species ◽  
Bv2 Cells ◽  
The Central Nervous System

GYY4137 is a hydrogen sulfide (H2S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H2S donor, Na2S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.

scholarly journals Reactive oxygen species production and discontinuous gas exchange in insects

2011 ◽  
Vol 279 (1730) ◽  
pp. 893-901 ◽  
Author(s):  
Leigh Boardman ◽  
John S. Terblanche ◽  
Stefan K. Hetz ◽  
Elrike Marais ◽  
Steven L. Chown
Keyword(s):  
Reactive Oxygen Species ◽  
Gas Exchange ◽  
Oxidative Damage ◽  
Negative Relationship ◽  
Reactive Oxygen ◽  
Organizational Level ◽  
Ros Production ◽  
Oxygen Species ◽  
Time Flow ◽  
Species Production

While biochemical mechanisms are typically used by animals to reduce oxidative damage, insects are suspected to employ a higher organizational level, discontinuous gas exchange mechanism to do so. Using a combination of real-time, flow-through respirometry and live-cell fluorescence microscopy, we show that spiracular control associated with the discontinuous gas exchange cycle (DGC) in Samia cynthia pupae is related to reactive oxygen species (ROS). Hyperoxia fails to increase mean ROS production, although minima are elevated above normoxic levels. Furthermore, a negative relationship between mean and mean ROS production indicates that higher ROS production is generally associated with lower . Our results, therefore, suggest a possible signalling role for ROS in DGC, rather than supporting the idea that DGC acts to reduce oxidative damage by regulating ROS production.

scholarly journals LncRNA TUG1 mediates ischemic myocardial injury by targeting miR-132-3p/HDAC3 axis

2020 ◽  
Vol 318 (2) ◽  
pp. H332-H344 ◽  
Author(s):  
Qiang Su ◽  
Yang Liu ◽  
Xiang-Wei Lv ◽  
Ri-Xin Dai ◽  
Xi-Heng Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Reactive Oxygen Species ◽  
Noncoding Rna ◽  
Ischemia Reperfusion ◽  
Ros Production ◽  
Oxygen Species ◽  
Histone Deacetylase 3 ◽  
Taurine Upregulated Gene 1

Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). In this study, we explored the functional significance and molecular mechanisms of TUG1/miR-132-3p axis in ischemia-challenged cardiomyocytes. In primary cardiomyocytes challenged with H2O2, expressions of miR-132-3p, TUG1, and other target proteins were measured by RT quantitative PCR or Western blot analysis; cell viability by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay; apoptosis by annexin V and propidium iodide staining; the abundance of acetylated H3K9 or histone deacetylase 3 (HDAC3) within the promoter of target genes by chromatin immunoprecipitation; the direct interaction between miR-132-3p and HDAC3 or TUG1 by luciferase reporter assay. The biological significance of miR-132-3p, TUG1, and HDAC3 was assessed using miR-132-3p mimic, siRNA-targeting TUG1 and HDAC3 inhibitor RGF966, respectively, in H2O2-challenged cells in vitro or ischemia-reperfusion (I/R)-induced AMI in vivo. miR-132-3p was downregulated, whereas TUG1 upregulated in H2O2-challenged cardiomyocytes. Overexpressing miR-132-3p or knocking down TUG1 significantly improved viability, inhibited apoptosis, and reduced ROS production in H2O2-stressed cardiomyocytes in vitro and alleviated I/R-induced AMI in vivo. Mechanistically, TUG1 sponged miR-132-3p and upregulated HDAC3, which reduced the acetylation of H3K9 and epigenetically inhibited expressions of antioxidative genes, including Bcl-xL, Prdx2, and Hsp70. The TUG1/miR-132-3p/HDAC3 axis critically regulates ROS production and the pathogenic development of AMI. Targeting TUG1, upregulating miR-132-3p, or inhibiting HDAC3 may benefit AMI treatment. NEW & NOTEWORTHY Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). However, the underlying mechanisms remain elusive. In the present study, we reported for the first time that H2O2 or ischemia-reperfusion-induced TUG1, by sponging microRNA 132-3p, activated histone deacetylase 3, which in turn targeted multiple protective genes, stimulated intracellular ROS accumulation, and aggravated the injury of AMI. Our findings might provide some insight to seek new targets for AMI treatment.

Oxidation of Potassium Channels in Neurodegenerative Diseases: A Mini- Review

2018 ◽  
Vol 17 (4) ◽  
pp. 267-271 ◽  
Author(s):  
Junsheng Yang ◽  
Xueni Yan
Keyword(s):  
Reactive Oxygen Species ◽  
Central Nervous System ◽  
Nervous System ◽  
Potassium Channels ◽  
Oxidative Damage ◽  
Neurodegenerative Diseases ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cell Functions ◽  
The Central Nervous System

Background & Objective: Increased level of reactive oxygen species is a hallmark of common neurodegenerative diseases such as Alzheimer’s Disease and Parkinson’s Disease. ROS can oxidize macromolecules including DNA, lipids and proteins and cause oxidative damage to the cell. Emerging evidence indicate that potassium channels in the central nervous system are no exceptions to these oxidative modifications. Conclusion: In this mini-review, we summarized recent reports on the oxidation of potassium channels in the CNS and the consequently resulted changes in cell functions and viability, with focus on its implications in neurodegenerative diseases.

scholarly journals In Vivo Imaging of Reactive Oxygen Species in Mouse Brain by using [3H]Hydromethidine as a Potential Radical Trapping Radiotracer

2014 ◽  
Vol 34 (12) ◽  
pp. 1907-1913 ◽  
Author(s):  
Kohji Abe ◽  
Nozomi Takai ◽  
Kazumi Fukumoto ◽  
Natsumi Imamoto ◽  
Misato Tonomura ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Production Model ◽  
Whole Body ◽  
Ros Production ◽  
Oxygen Species ◽  
Radical Trapping ◽  
The Brain

To assess reactive oxygen species (ROS) production by detecting the fluorescent oxidation product, hydroethidine has been used extensively. The present study was undertaken to evaluate the potential of the hydroethidine derivative as a radiotracer to measure in vivo brain ROS production. [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]Hydromethidine) was synthesized, and evaluated using in vitro radical-induced oxidization and in vivo brain ROS production model. In vitro studies have indicated that [3H]Hydromethidine is converted to oxidized products by a superoxide radical (O2• -) and a hydroxyl radical (OH• -) but not hydrogen peroxide (H2O2). In vivo whole-body distribution study showed that [3H]Hydromethidine rapidly penetrated the brain and then was washed out in normal mice. Microinjection of sodium nitroprusside (SNP) into the brain was performed to produce ROS such as OH• - via Fenton reaction. A significant accumulation of radioactivity immediately after [3H]Hydromethidine injection was seen in the side of the brain treated with SNP (5 and 20 nmol) compared with that in the contralateral side. These results indicated that [3H]Hydromethidine freely penetrated into the brain where it was rapidly converted to oxidized forms, which were trapped there in response to the production of ROS. Thus, [3H]Hydromethidine should be useful as a radical trapping radiotracer in the brain.

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