scholarly journals PRG5 Knockout Precipitates Late-Onset Hypersusceptibility to Pilocarpine-Induced Juvenile Seizures by Exacerbating Hippocampal Zinc Signaling-Mediated Mitochondrial Damage

2021 ◽  
Vol 15 ◽  
Author(s):  
Dandan Wang ◽  
Mei-fang Jin ◽  
Lili Li ◽  
Yueying Liu ◽  
Yuxiao Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Mossy Fiber ◽  
Gene Knockout ◽  
Membrane Integrity ◽  
Zinc Ion ◽  
Seizure Threshold ◽  
Neuronal Cultures ◽  
Ion Content ◽  
Zinc Signaling

IntroductionEpileptogenesis is understood as the plastic process that produces a persistent reorganization of the brain’s neural network after a precipitating injury (recurrent neonatal seizures, for instance) with a latent period, finally leading to neuronal hyperexcitability. Plasticity-related genes (PRGs), also known as lipid phosphate phosphatase-related proteins (PLPPRs), are regulators of mitochondrial membrane integrity and energy metabolism. This study was undertaken to determine whether PRG5 gene knockout contributes to the delayed hypersensitivity induced by developmental seizures and the aberrant sprouting of hippocampal mossy fibers, and to determine whether it is achieved through the mitochondrial pathway. Here, we developed a “twist” seizure model by coupling pilocarpine-induced juvenile seizures with later exposure to penicillin to test the long-term effects of PRG5 knockout on seizure latency through comparison with wild-type (WT) mice. Hippocampal mossy fiber sprouting (MFS) was detected by Timm staining. In order to clarify the mechanism of the adverse reactions triggered by PRG5 knockout, hippocampal HT22 neuronal cultures were exposed to glutamate, with or without PRG5 interference. Mitochondrial function, oxidative stress indicators and zinc ion content were detected.ResultsPRG5 gene knockout significantly reduced the seizure latency, and aggravated the lowered seizure threshold induced by developmental seizures. Besides, knockout of the PRG5 gene reduced the MFS scores to a certain extent. Furthermore, PRG5 gene silencing significantly increases the zinc ion content in hippocampal neurons, impairs neuronal activity and mitochondrial function, and exacerbates glutamate-induced oxidative stress damage.ConclusionIn summary, PRG5 KO is associated with significantly greater hypersusceptibility to juvenile seizures in PRG5(–/–) mice compared with WT mice. These effects may be related to the hippocampal zinc signaling. The effects do not appear to be related to changes in MFS because KO mice with juvenile seizures had the shortest seizure latencies but exhibited less MFS than WT mice with juvenile seizures.

Cytotoxicity and metabolic stress induced by acetaldehyde in human intestinal LS174T goblet-like cells

2014 ◽  
Vol 307 (3) ◽  
pp. G286-G294 ◽  
Author(s):  
Elhaseen Elamin ◽  
Ad Masclee ◽  
Freddy Troost ◽  
Jan Dekker ◽  
Daisy Jonkers
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Membrane Integrity ◽  
Reactive Oxygen Species Generation ◽  
Intestinal Barrier ◽  
Atp Depletion ◽  
Intestinal Barrier Function ◽  
Double Labeling ◽  
Ldh Release ◽  
Negative Controls

There is compelling evidence indicating that ethanol and its oxidative metabolite acetaldehyde can disrupt intestinal barrier function. Apart from the tight junctions, mucins secreted by goblet cells provide an effective barrier. Ethanol has been shown to induce goblet cell injury associated with alterations in mucin glycosylation. However, effects of its most injurious metabolite acetaldehyde remain largely unknown. This study aimed to assess short-term effects of acetaldehyde (0, 25, 50, 75, 100 μM) on functional characteristics of intestinal goblet-like cells (LS174T). Oxidative stress, mitochondrial function, ATP, and intramitochondrial calcium (Ca2+) were assessed by dichlorofluorescein, methyltetrazolium, and bioluminescence, MitoTracker green and rhod-2 double-labeling. Membrane integrity and apoptosis were evaluated by measuring lactate dehydrogenase (LDH), caspase 3/7, and cleavage of cytokeratin 18 (CK18). Expression of mucin 2 (MUC2) was determined by cell-based ELISA. Acetaldehyde significantly increased reactive oxygen species generation and decreased mitochondrial function compared with negative controls ( P < 0.05). In addition, acetaldehyde dose-dependently decreased ATP levels and induced intramitochondrial Ca2+ accumulation compared with negative controls ( P < 0.05). Furthermore, acetaldehyde induced LDH release and increased caspase3/7 activity and percentage of cells expressing cleaved CK18 and increased MUC2 protein expression compared with negative controls ( P < 0.0001). ATP depletion and LDH release could be largely prevented by the antioxidant N-acetylcysteine, suggesting a pivotal role for oxidative stress. Our data demonstrate that acetaldehyde has distinct oxidant-dependent metabolic and cytotoxic effects on LS174T cells that can lead to induction of cellular apoptosis. These effects may contribute to acetaldehyde-induced intestinal barrier dysfunction and subsequently to liver injury.

scholarly journals Glycine ameliorates mitochondrial dysfunction caused by ABT-199 in porcine oocytes

2021 ◽  
Author(s):  
Sicong Yu ◽  
Lepeng Gao ◽  
Yang Song ◽  
Xin Ma ◽  
Shuang Liang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Oocyte Maturation ◽  
Mitochondrial Function ◽  
Protective Action ◽  
Damage Model ◽  
Developmental Competence ◽  
Free Calcium ◽  
Maturation In Vitro

Abstract Mitochondria play an important role in controlling oocyte developmental competence. Our previous studies showed that glycine can regulate mitochondrial function and improve oocyte maturation in vitro. However, the mechanisms by which glycine affects mitochondrial function during oocyte maturation in vitro have not been fully investigated. In this study, we induced a mitochondrial damage model in oocytes with the Bcl-2-specific antagonist ABT-199. We investigated whether glycine could reverse the mitochondrial dysfunction induced by ABT-199 exposure and whether it is related to calcium regulation. Our results showed that ABT-199 inhibited cumulus expansion, decreased the oocyte maturation rate and the intracellular glutathione (GSH) level, caused mitochondrial dysfunction, induced oxidative stress, which was confirmed by decreased mitochondrial membrane potential (Δ⍦m) and the expression of mitochondrial function-related genes (PGC-1α), and increased reactive oxygen species (ROS) levels and the expression of apoptosis-associated genes (Bax, caspase-3, CytC). More importantly, ABT-199-treated oocytes showed an increase in the intracellular free calcium concentration ([Ca 2+]i) and had impaired cortical type 1 inositol 1,4,5-trisphosphate receptors (IP3R1) distribution. Nevertheless, treatment with glycine significantly ameliorated mitochondrial dysfunction, oxidative stress and apoptosis, glycine also regulated [Ca 2+]i levels and IP3R1 cellular distribution, which further protects oocyte maturation in ABT-199-induced porcine oocytes. Taken together, our results indicate that glycine has a protective action against ABT-199-induced mitochondrial dysfunction in porcine oocytes.

scholarly journals Physiological, Morphological and Antioxidant Responses of Pediococcus pentosaceus R1 and Lactobacillus fermentum R6 Isolated from Harbin Dry Sausages to Oxidative Stress

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1203
Author(s):  
Huan Zhang ◽  
Jianhang Xu ◽  
Qian Chen ◽  
Hui Wang ◽  
Baohua Kong
Keyword(s):  
Oxidative Stress ◽  
Electron Microscopy ◽  
Antioxidant Properties ◽  
Membrane Integrity ◽  
Starter Cultures ◽  
Lactobacillus Fermentum ◽  
Fermented Foods ◽  
Pediococcus Pentosaceus ◽  
Cell Membrane Integrity ◽  
Dry Sausages

As functional starter cultures and potential probiotics, the ability of lactic acid bacteria to resist oxidative stress is essential to maintain viability and functional properties. This study investigates the effects of H2O2 at different concentrations (0, 1, 2, and 3 mM) on the physiological, morphological, and antioxidant properties of Pediococcus pentosaceus R1 and Lactobacillus fermentum R6 isolated from Harbin dry sausages. The increase in H2O2 concentration induced a significant increase in reactive oxygen species and a decrease in intracellular ATP levels (p < 0.05). Based on scanning electron microscopy, transmission electron microscopy, and electric conductivity analysis, H2O2 stress caused cell deformation, the destruction of cell membrane integrity, partial loss of the cytoplasm, and an increase in the cell conductivity of both strains. H2O2 stress with 1 mM or 2 mM concentrations could effectively improve the scavenging rates of free radicals, the activities of superoxide dismutase and glutathione peroxide, and the total antioxidant capacity of both strains (p < 0.05). In conclusion, an appropriate oxidative stress contributed to the activation of the antioxidant defense system of both strains, conferred strains a better effect in inhibiting the oxidation of fermented foods, and improved the health of the host.

scholarly journals Effect of Lead and Copper on Photosynthetic Apparatus in Citrus (Citrus aurantium L.) Plants. The Role of Antioxidants in Oxidative Damage as a Response to Heavy Metal Stress

Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 155
Author(s):  
Anastasia Giannakoula ◽  
Ioannis Therios ◽  
Christos Chatzissavvidis
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Heavy Metal ◽  
Metal Tolerance ◽  
Heavy Metal Tolerance ◽  
Membrane Integrity ◽  
Photosynthetic Apparatus ◽  
Heavy Metal Stress ◽  
Photosynthetic Parameters ◽  
Citrus Aurantium

Photosynthetic changes and antioxidant activity to oxidative stress were evaluated in sour orange (Citrus aurantium L.) leaves subjected to lead (Pb), copper (Cu) and also Pb + Cu toxicity treatments, in order to elucidate the mechanisms involved in heavy metal tolerance. The simultaneous effect of Pb− and Cu on growth, concentration of malondialdehyde (MDA), hydrogen peroxide (H2O2), chlorophylls, flavonoids, carotenoids, phenolics, chlorophyll fluorescence and photosynthetic parameters were examined in leaves of Citrus aurantium L. plants. Exogenous application of Pb and Cu resulted in an increase in leaf H2O2 and lipid peroxidation (MDA). Toxicity symptoms of both Pb and Cu treated plants were stunted growth and decreased pigments concentration. Furthermore, photosynthetic activity of treated plants exhibited a significant decline. The inhibition of growth in Pb and Cu-treated plants was accompanied by oxidative stress, as indicated by the enhanced lipid peroxidation and the high H2O2 concentration. Furthermore, antioxidants in citrus plants after exposure to high Pb and Cu concentrations were significantly increased compared to control and low Pb and Cu treatments. In conclusion, this study indicates that Pb and Cu promote lipid peroxidation, disrupt membrane integrity, reduces growth and photosynthesis and inhibit mineral nutrition. Considering the potential for adverse human health effects associated with high concentrations of Pb and Cu contained in edible parts of citrus plants the study signals that it is important to conduct further research into the accessibility and uptake of the tested heavy metals in the soil and whether they pose risks to humans.

scholarly journals Prolonged α-Tocopherol Deficiency Decreases Oxidative Stress and Unmasks α-Tocopherol-dependent Regulation of Mitochondrial Function in the Brain

2008 ◽  
Vol 283 (11) ◽  
pp. 6915-6924 ◽  
Author(s):  
Sarah L. Cuddihy ◽  
Sameh S. Ali ◽  
Erik S. Musiek ◽  
Jacinta Lucero ◽  
Sarah J. Kopp ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
The Brain

scholarly journals Oxidative Stress Induces Dephosphorylation of τ in Rat Brain Primary Neuronal Cultures

2002 ◽  
Vol 68 (4) ◽  
pp. 1590-1597 ◽  
Author(s):  
Daniel R. Davis ◽  
Brian H. Anderton ◽  
Jean-Pierre Brion ◽  
C. Hugh Reynolds ◽  
Diane P. Hanger
Keyword(s):  
Oxidative Stress ◽  
Rat Brain ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures

scholarly journals Acetyl-l-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity

1998 ◽  
Vol 95 (16) ◽  
pp. 9562-9566 ◽  
Author(s):  
Tory M. Hagen ◽  
Russell T. Ingersoll ◽  
Carol M. Wehr ◽  
Jens Lykkesfeldt ◽  
Vladimir Vinarsky ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Activity ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Ambulatory Activity ◽  
General Measure ◽  
Cellular Oxygen ◽  
Old Rats ◽  
Oxidant Production ◽  
Parenchymal Cells

Mitochondrial function and ambulatory activity were monitored after feeding old rats acetyl-l-carnitine (ALCAR). Young (3–5 mo) and old (22–28 mo) rats were given a 1.5% (wt/vol) solution of ALCAR in their drinking water for 1 mo, were sacrificed, and their liver parenchymal cells were isolated. ALCAR supplementation significantly reverses the age-associated decline of mitochondrial membrane potential, as assessed by rhodamine 123 staining. Cardiolipin, which declines significantly with age, is also restored. ALCAR increases cellular oxygen consumption, which declines with age, to the level of young rats. However, the oxidant production per oxygen consumed, as measured by 2′,7′-dichlorofluorescin fluorescence levels, is ≈30% higher than in untreated old rats. Cellular glutathione and ascorbate levels were nearly 30% and 50% lower, respectively, in cells from ALCAR-supplemented old rats than in untreated old rats, further indicating that ALCAR supplementation might increase oxidative stress. Ambulatory activity in young and old rats was quantified as a general measure of metabolic activity. Ambulatory activity, defined as mean total distance traveled, in old rats is almost 3-fold lower than in young animals. ALCAR supplementation increases ambulatory activity significantly in both young and old rats, with the increase being larger in old rats. Thus, ALCAR supplementation to old rats markedly reverses the age-associated decline in many indices of mitochondrial function and general metabolic activity, but may increase oxidative stress.

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