Journal: The FASEB Journal

Article Title: The role of mitochondrial oxidative stress in the metabolic alterations in diet-induced obesity in rats

doi: 10.1096/fj.201900347RR

Figure Lengend Snippet: Protein levels of mitochondrial complexes I-V (A), Cyclo F (B), MFN1 (C), and protein disulfide isomerize family A member 6 (D) in EAT from control rats fed a CT and rats fed an HFD treated with vehicle or with the mitochondrial antioxidant MitoQ (MQ; 200 µM). Bar graphs represent the means ± sd of 6–8 animals normalized to for reference housekeeping. *P < 0.05, **P < 0.01, ***P < 0.001 vs. control group, †P < 0.05, ††P < 0.01 vs. HFD group.

Article Snippet: Open in a separate window Figure 5 Protein levels of mitochondrial complexes I-V ( A ), Cyclo F ( B ), MFN1 ( C ), and protein disulfide isomerize family A member 6 ( D ) in EAT from control rats fed a CT and rats fed an HFD treated with vehicle or with the mitochondrial antioxidant MitoQ (MQ; 200 μM).

Techniques: Control

Journal: PLoS ONE

Article Title: Dopamine Induced Neurodegeneration in a PINK1 Model of Parkinson's Disease

doi: 10.1371/journal.pone.0037564

Figure Lengend Snippet: a: Dopamine induces a rise in cytosolic ROS production in wt neurons, in the presence of inhibitor of NADPH oxidase, 0.5 µM DPI. Dopamine induced ROS production was prevented by application of the MAO inhibitor, 20 µM selegiline. b: Dopamine induced a similar rise in ROS production in PINK1 ko neurons, which is partially inhibited by the application of MAO inhibitor, selegiline. c: Histogram demonstrating the increase in ROS production in PINK1 ko neurons compared to wt neurons, and the dopamine induced increase in ROS in both wt and PINK1 ko neurons. The dopamine induced increase in ROS may be reduced in both wt and PINK1 ko neurons by application of selegiline. d: Application of an inhibitor of NADPH oxidase, DPI, partially prevented dopamine induced mitochondrial depolarisation in PINK1 ko neurons. e: Application of mitochondrially located antioxidant, MitoQ, partially prevented dopamine induced mitochondrial depolarisation in PINK1 ko neurons. f: Application of MAO inhibitor, selegiline, completely prevented the dopamine induced mitochondrial depolarisation in PINK1 ko neurons. g: Histogram demonstrating the effect of antioxidants, verapamil, and dopamine receptor antagonists on the dopamine-induced calcium signal in PINK1 ko astrocytes and neurons. The effect of dopamine on the calcium signal (fura-2 ratio) was normalised to 1.0. Selegiline has a selective effect in reducing the calcium signal in astrocytes, while verapamil has a selective effect in reducing the calcium signal in neurons.

Article Snippet: Pre-incubation of cells with the mitochondrially localised antioxidant MitoQ (10 μM) prevented the dopamine induced mitochondrial depolarisation in PINK1 ko neurons (dopamine-induced depolarisation reduced from 58.8±14% to 21.3±3.7%; n = 42; p<0.001; ).

Techniques:

Journal: PLoS ONE

Article Title: Dopamine Induced Neurodegeneration in a PINK1 Model of Parkinson's Disease

doi: 10.1371/journal.pone.0037564

Figure Lengend Snippet: a: Application of 5 mM pyruvate reduced the dopamine induced mitochondrial depolarisation, but did not completely prevent it. b: Dopamine induced a rise in mitochondrial superoxide in PINK1 ko neurons, but not in wt neurons. 5 mM pyruvate and 5 mM Me-succinate both reduced the dopamine-induced mitochondrial ROS production. c: Histogram comparing the reduction of dopamine induced mitochondrial depolarisation by different compounds: the PTP inhibitor CsA, calcium chelator BAPTA-AM, NADPH oxidase inhibitor DPI, mitochondrial antioxidant MitoQ, MAO inhibitor selegiline, respiratory chain substrates pyruvate and me-succinate, and the calcium channel blocker verapamil all resulted in a statistically significant reduction in dopamine induced mitochondrial depolarisation in PINK1 ko neurons.

Article Snippet: Pre-incubation of cells with the mitochondrially localised antioxidant MitoQ (10 μM) prevented the dopamine induced mitochondrial depolarisation in PINK1 ko neurons (dopamine-induced depolarisation reduced from 58.8±14% to 21.3±3.7%; n = 42; p<0.001; ).

Techniques:

Journal: Frontiers in Immunology

Article Title: Oxidative Stress Following Intracerebral Hemorrhage: From Molecular Mechanisms to Therapeutic Targets

doi: 10.3389/fimmu.2022.847246

Figure Lengend Snippet: The primary sources of ROS/RNS following ICH. Following ICH, the destruction of erythrocytes in a hematoma releases hemoglobin and heme. The RBC and degraded hemoglobin and heme are phagocyted by microglia/macrophages. Hemoglobin is then oxidized to methemoglobin to generate free radicals. Heme is metabolized by heme oxygenase into biliverdin, iron and carbonic oxide. Iron is transferred to neurons mediated by the transferrin delivery system, where iron reacts with H 2 O 2 through the Fenton reaction to produce •OH, which is more toxic. The opening of inner membrane anion channels and mitochondrial permeability transition pore results in ROS release. Besides, excessive glutamate following ICH activates postsynaptic neuron NMDA receptors, promotes Ca 2+ influx and intracellular Ca 2+ overload, triggering the synthesis of neuronal nitric oxide and superoxide via activating neuronal nitric oxide synthase and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) respectively. The polymerization of nitric oxide and superoxide forms peroxynitrite. Moreover, NOX in microglia/macrophages is activated to generate O 2 · and NOS converts L-arginine to L-citrulline to produces NO. HO, heme oxygenase; Hb, hemoglobin; H 2 O 2 , hydrogen peroxide; •OH, hydroxyl radical; ICH, intracerebral hemorrhage; IMAC, inner membrane anion channel; mPTP, mitochondrial permeability transition pore; NOXs, nicotinamide adenine dinucleotide phosphate oxidases; NO, nitric oxide; NOS, nitric oxide synthase; ONOO, peroxynitrite; RBC, red blood cell; ROS/RNS, reactive oxygen/nitrogen species; O 2 ·, superoxide anion radical; Tf, transferrin.

Article Snippet: In addition, blocking overproduction of mitochondrial ROS through a selective mitochondrial ROS antioxidant MitoQ reduces the NLRP3 inflammasome activation in FeCl 2 -treated microglia ( ).

Techniques: Membrane, Permeability

Journal: Frontiers in Immunology

Article Title: Oxidative Stress Following Intracerebral Hemorrhage: From Molecular Mechanisms to Therapeutic Targets

doi: 10.3389/fimmu.2022.847246

Figure Lengend Snippet: The main destructive effect of OS to brain following ICH. The production of ROS/RNS significantly exceeds the body’s antioxidant capacity after ICH, resulting in irreversible damage to lipids, proteins, and DNA, ultimately inducing multiple forms of cell death pathways (apoptosis, necrosis, necroptosis, ferroptosis and autophagy) via activating related molecular networks or genes. Besides, OS increases the level of NF-κB, which upregulates proinflammatory cytokines, inflammatory molecules and MMPs to result in inflammation. MMPs increase the permeability of capillaries by degrading the basement membrane and tight junction structure of cerebrovascular endothelial cells, thereby contributing to inflammation and BBB disruption. Moreover, OS can directly injure endothelial cells and damage the BBB. BBB, blood brain barrier; MMPs, matrix metalloproteinases; mPTP, mitochondrial permeability transition pore; NF-κB, nuclear factor-kappa B; SBI, secondary brain injury.

Article Snippet: In addition, blocking overproduction of mitochondrial ROS through a selective mitochondrial ROS antioxidant MitoQ reduces the NLRP3 inflammasome activation in FeCl 2 -treated microglia ( ).

Techniques: Permeability, Membrane, Disruption