L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency

L-Arginine (L-ARG) supplementation has been suggested as a therapeutic option in several diseases, including Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS), arguably the most common mitochondrial disease. It is suggested that L-ARG, a nitric oxide (NO) precursor, can restore NO levels in blood vessels, improving cerebral blood flow. However, NO also participates in mitochondrial processes, such as mitochondrial biogenesis, the regulation of the respiratory chain, and oxidative stress. This study investigated the effects of L-ARG on mitochondrial function, nitric oxide synthesis, and nitro-oxidative stress in cell lines harboring the MELAS mitochondrial DNA (mtDNA) mutation (m.3243A>G). We evaluated mitochondrial enzyme activity, mitochondrial mass, NO concentration, and nitro-oxidative stress. Our results showed that m.3243A>G cells had increased NO levels and protein nitration at basal conditions. Treatment with L-ARG did not affect the mitochondrial function and mass but reduced the intracellular NO concentration and nitrated proteins in m.3243A>G cells. The same treatment led to opposite effects in control cells. In conclusion, we showed that the main effect of L-ARG was on protein nitration. Lowering protein nitration is probably involved in the mechanism related to L-ARG supplementation benefits in MELAS patients.

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Effects of GH/IGF on the Aging Mitochondria

Cells ◽

10.3390/cells9061384 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1384 ◽

Cited By ~ 1

Author(s):

Sher Bahadur Poudel ◽

Manisha Dixit ◽

Maria Neginskaya ◽

Karthik Nagaraj ◽

Evgeny Pavlov ◽

...

Keyword(s):

Oxidative Stress ◽

Growth Hormone ◽

Cell Differentiation ◽

Growth Factor ◽

Mitochondrial Biogenesis ◽

Mitochondrial Function ◽

Cellular Aging ◽

Mitochondrial Mass ◽

Atp Production ◽

And Function

The mitochondria are key organelles regulating vital processes in the eukaryote cell. A decline in mitochondrial function is one of the hallmarks of aging. Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are somatotropic hormones that regulate cellular homeostasis and play significant roles in cell differentiation, function, and survival. In mammals, these hormones peak during puberty and decline gradually during adulthood and aging. Here, we review the evidence that GH and IGF-1 regulate mitochondrial mass and function and contribute to specific processes of cellular aging. Specifically, we discuss the contribution of GH and IGF-1 to mitochondrial biogenesis, respiration and ATP production, oxidative stress, senescence, and apoptosis. Particular emphasis was placed on how these pathways intersect during aging.

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Atomoxetine produces oxidative stress and alters mitochondrial function in human neuron-like cells

Scientific Reports ◽

10.1038/s41598-019-49609-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Juan Carlos Corona ◽

Sonia Carreón-Trujillo ◽

Raquel González-Pérez ◽

Denise Gómez-Bautista ◽

Daniela Vázquez-González ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Mitochondrial Function ◽

Reactive Oxygen ◽

Therapeutic Effects ◽

Oxygen Species ◽

Mitochondrial Reactive Oxygen Species ◽

Mitochondrial Mass ◽

Norepinephrine Reuptake Inhibitor ◽

Norepinephrine Reuptake

Abstract Atomoxetine (ATX) is a non-stimulant drug used in the treatment of attention-deficit/hyperactivity disorder (ADHD) and is a selective norepinephrine reuptake inhibitor. It has been shown that ATX has additional effects beyond the inhibition of norepinephrine reuptake, affecting several signal transduction pathways and alters gene expression. Here, we study alterations in oxidative stress and mitochondrial function in human differentiated SH-SY5Y cells exposed over a range of concentrations of ATX. We found that the highest concentrations of ATX in neuron-like cells, caused cell death and an increase in cytosolic and mitochondrial reactive oxygen species, and alterations in mitochondrial mass, membrane potential and autophagy. Interestingly, the dose of 10 μM ATX increased mitochondrial mass and decreased autophagy, despite the induction of cytosolic and mitochondrial reactive oxygen species. Thus, ATX has a dual effect depending on the dose used, indicating that ATX produces additional active therapeutic effects on oxidative stress and on mitochondrial function beyond the inhibition of norepinephrine reuptake.

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Mitochondrial Dysfunction Is Involved in Apoptosis Induced by Serum Withdrawal and Fatty Acids in the β-Cell Line Ins-1

Endocrinology ◽

10.1210/en.2001-211282 ◽

2003 ◽

Vol 144 (1) ◽

pp. 335-345 ◽

Cited By ~ 132

Author(s):

Isabel Maestre ◽

Joaquín Jordán ◽

Soledad Calvo ◽

Juan Antonio Reig ◽

Valentín Ceña ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Fatty Acids ◽

Cytochrome C ◽

Mitochondrial Function ◽

Marginal Effect ◽

Β Cell ◽

Apoptosis Process ◽

Apoptosis Inducing Factor ◽

Factor Release

Abstract The potential toxic effects of high extracellular concentrations of fatty acids were tested in β(INS-1)-cells cultured in the absence of serum, a condition known to alter cell survival in various systems. This may in part mimic the situation in type 1 or 2 diabetes where β-cells are already insulted by various stressful conditions, such as cytokines and oxidative stress. Serum removal caused, over a 36-h period, oxidative stress and an early impairment of mitochondrial function, as revealed by increased superoxide production and markedly reduced mitochondrial membrane potential, but a lack of cytochrome c and apoptosis-inducing factor release in the cytosol. The fatty acids palmitate and oleate considerably accelerated the apoptosis process in serum-starved cells, as revealed by fluorescence-activated cell sorting analysis, morphological changes, chromatin condensation, DNA laddering, poly(ADP-ribose) polymerase cleavage, cytochrome c and apoptosis-inducing factor release, and increased levels of Bax and cytosolic caspase-2. The fatty acids also increased nitric oxide production, apparently independently of inducible nitric oxide synthase induction. Under the same experimental conditions, elevated glucose alone had only a marginal effect on β-cell apoptosis. Together the results indicate that elevated concentrations of fatty acids are particularly efficient in accelerating the rate of apoptosis of already stressed β(INS-1)-cells displaying altered mitochondrial function, and that the mitochondrial arm of the apoptosis process is involved in β-cell lipotoxicity.

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Protein nitration as footprint of oxidative stress-related nitric oxide signaling pathways in developing Ciona intestinalis

Nitric Oxide ◽

10.1016/j.niox.2012.03.012 ◽

2012 ◽

Vol 27 (1) ◽

pp. 18-24 ◽

Cited By ~ 9

Author(s):

Elena Ercolesi ◽

Gabriella Tedeschi ◽

Gabriella Fiore ◽

Armando Negri ◽

Elisa Maffioli ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Signaling Pathways ◽

Ciona Intestinalis ◽

Protein Nitration ◽

Nitric Oxide Signaling

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In vivo and in vitro approaches demonstrate proline is not directly involved in the protection against superoxide, nitric oxide, nitrogen dioxide and peroxynitrite

Functional Plant Biology ◽

10.1071/fp16060 ◽

2016 ◽

Vol 43 (9) ◽

pp. 870 ◽

Cited By ~ 27

Author(s):

Santiago Signorelli ◽

Camila Imparatta ◽

Marta Rodríguez-Ruiz ◽

Omar Borsani ◽

Francisco J. Corpas ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Nitrogen Dioxide ◽

Time Course ◽

Nitrosative Stress ◽

Lotus Japonicus ◽

Protein Nitration ◽

Course Content

Plants accumulate proline under diverse types of stresses, and it has been suggested that this α-amino acid has the capacity to protect against oxidative stress. However, it is still controversial whether its protection is due to the direct scavenging of reactive oxygen species (ROS). To solve this issue and considering that nitrosative stress is directly related with an oxidative stress condition, we evaluated whether proline can protect against nitrosative damage. Using proteins of Lotus japonicus (Regel) K.Larsen leaves exposed to a peroxynitrite (ONOO–/ONOOH) generator in presence and absence of 100mM proline, the potential of proline to protect was analysed by the protein nitration profile and NADP-dependent isocitrate dehydrogenase activity, which is inhibited by nitration. In both cases, the presence of proline did not diminish the peroxynitrite effects. Additionally, proline biosynthesis Arabidopsis knockout (KO) mutant plants of Δ(1)-pyrroline-5-carboxylate synthetase1 (P5CS1) gene, designated as Atp5cs1-1 and Atp5cs1-4, showed similar protein nitration levels as wild-type plants under salinity-induced oxidative stress, despite mutants having higher levels of lipid oxidation, H2O2 and superoxide (O2·–). Finally, by a fluorometric assay using specific fluorescent probes, it was determined that the presence of 100mM proline did not affect the time-course content of peroxynitrite or nitric oxide generation in vitro. Our results reveal the relevance of proline accumulation in vivo under stress, but unequivocally demonstrate that proline is not a direct scavenger of peroxynitrite, superoxide, ·NO and nitrogen dioxide (·NO2).

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Plasma membrane oxidoreductase activity in cultured cells in relation to mitochondrial function and oxidative stress

BioFactors ◽

10.1002/biof.5520200408 ◽

2004 ◽

Vol 20 (4) ◽

pp. 265-272 ◽

Cited By ~ 6

Author(s):

Giulia Deleonardi ◽

Annalisa Biondi ◽

Marilena D'Aurelio ◽

Milena Merlo Pich ◽

Karmen Stankov ◽

...

Keyword(s):

Oxidative Stress ◽

Plasma Membrane ◽

Mitochondrial Function ◽

Cultured Cells ◽

Oxidoreductase Activity ◽

And Oxidative Stress

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Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

Current Pharmaceutical Design ◽

10.2174/1381612826666200408101550 ◽

2020 ◽

Vol 26 (22) ◽

pp. 2610-2619 ◽

Cited By ~ 2

Author(s):

Tarique Hussain ◽

Ghulam Murtaza ◽

Huansheng Yang ◽

Muhammad S. Kalhoro ◽

Dildar H. Kalhoro

Keyword(s):

Oxidative Stress ◽

Chronic Diseases ◽

Inflammatory Diseases ◽

Therapeutic Option ◽

Cellular Level ◽

Antiinflammatory Drugs ◽

Suitable Alternative ◽

Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

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MiR-485-5p Promotes Neuron Survival through Mediating Rac1/Notch2 Signaling Pathway after Cerebral Ischemia/Reperfusion

Current Neurovascular Research ◽

10.2174/1567202617666200415154822 ◽

2020 ◽

Vol 17 (3) ◽

pp. 259-266 ◽

Cited By ~ 2

Author(s):

Xuan Chen ◽

Sumei Zhang ◽

Peipei Shi ◽

Yangli Su ◽

Dong Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Therapeutic Option ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Small Gtpase ◽

Luciferase Reporter ◽

Pathological Feature ◽

In Cells

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

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Astaxanthin, the Natural Antioxidant, Reduces Reserpine Induced Depression in Mice

Current Bioactive Compounds ◽

10.2174/1573407216666200203142722 ◽

2020 ◽

Vol 16 (9) ◽

pp. 1319-1327

Author(s):

Ferdous Khan ◽

Syed A. Kuddus ◽

Md. H. Shohag ◽

Hasan M. Reza ◽

Murad Hossain

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Reduced Glutathione ◽

Forced Swim Test ◽

Tail Suspension Test ◽

Glutathione Depletion ◽

Swim Test ◽

Stress Markers ◽

Immobility Time ◽

Biochemical Level

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

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