scholarly journals Accumulation of Exogenous Amyloid-BetaPeptide in Hippocampal Mitochondria Causes Their Dysfunction: A Protective Role for Melatonin

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Sergio Rosales-Corral ◽  
Dario Acuna-Castroviejo ◽  
Dun Xian Tan ◽  
Gabriela López-Armas ◽  
José Cruz-Ramos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Membrane ◽  
Respiratory Control ◽  
Hydrolytic Activity ◽  
Protective Role ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Respiratory Control Ratio ◽  
Inner Mitochondrial Membrane ◽  
Subcellular Structure

Amyloid-beta(Aβ) pathology is related to mitochondrial dysfunction accompanied by energy reduction and an elevated production of reactive oxygen species (ROS). Monomers and oligomers of Aβ have been found inside mitochondria where they accumulate in a time-dependent manner as demonstrated in transgenic mice and in Alzheimer’s disease (AD) brain. We hypothesize that the internalization of extracellular Aβ aggregates is the major cause of mitochondrial damage and here we report that following the injection of fibrillar Aβ into the hippocampus, there is severe axonal damage which is accompanied by the entrance of Aβ into the cell. Thereafter, Aβ appears in mitochondria where it is linked to alterations in the ionic gradient across the inner mitochondrial membrane. This effect is accompanied by disruption of subcellular structure, oxidative stress, and a significant reduction in both the respiratory control ratio and in the hydrolytic activity of ATPase. Orally administrated melatonin reduced oxidative stress, improved the mitochondrial respiratory control ratio, and ameliorated the energy imbalance.

scholarly journals Monoamine Oxidases as Potential Contributors to Oxidative Stress in Diabetes: Time for a Study in Patients Undergoing Heart Surgery

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Oana M. Duicu ◽  
Rodica Lighezan ◽  
Adrian Sturza ◽  
Raluca A. Ceausu ◽  
Claudia Borza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Membrane ◽  
Ventricular Hypertrophy ◽  
Heart Surgery ◽  
Experimental Studies ◽  
Oxygen Species ◽  
Inner Mitochondrial Membrane ◽  
Monoamine Oxidases ◽  
The Past

Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs) at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction. This paper addresses the contribution of mitochondrial dysfunction to the pathogenesis of heart failure and diabetes together with the mounting evidence for an emerging role of MAO inhibition as putative cardioprotective strategy in both conditions.

Abstract 243: The Role of Reactive Oxygen Species in Hyperglycemia-Induced Attenuation of Anesthetic Preconditioning in Induced Pluripotent Stem Cell-Derived Cardiomyocytes

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Scott Canfield ◽  
Danielle Twaroski ◽  
Xiaowen Bai ◽  
Chika Kikuchi ◽  
Zeljko J Bosnjak
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Membrane Potential ◽  
Lactate Dehydrogenase ◽  
Mitochondrial Membrane ◽  
Oxygen Species ◽  
Anesthetic Preconditioning ◽  
Induced Pluripotent ◽  
Type 2 Diabetic

Anesthetic Preconditioning (APC) protects the myocardium from ischemia/reperfusion injury. The cardioprotective effects of APC is diminished or even eliminated in individuals with diabetes mellitus and/or hyperglycemia. The development of patient-specific induced pluripotent stem cells and their differentiation capability has provided us with an in vitro model to study the inefficiency of APC in these individuals.To investigate the underlying mechanisms involved in the attenuation of APC in both diabetic individuals and in hyperglycemia we utilized cardiomyocytes derived from Type 2 diabetic patient and healthy individual iPSCs, (T2DM-iPSCs and N-iPSCs, respectively). Contracting cardiomyocytes were dissociated and selected by the expression of green fluorescent protein under the transcriptional control of myosin light chain-2v. Cardiomyocytes were exposed to varying glucose concentrations (5, 11, and 25 mM). Lactate dehydrogenase (LDH) release was measured using a colorimetric cytotoxicity assay kit and read spectrophotometrically. Mitochondrial membrane potential and reactive oxygen species (ROS) generation were measured with confocal microscopy. APC reduced oxidative stress-induced lactate dehydrogenase (LDH) release in cardiomyocytes derived from both N-iPSCs- and T2DM-iPSCs in 5 and 11 mM glucose concentrations, but not in 25 mM glucose. Baseline membrane potential was similar between non-diabetic- and Type 2 diabetic-derived cardiomyocytes; however 25 mM glucose hyperpolarized the mitochondrial membrane potential. T2DM-iPSC-derived cardiomyocytes had an increase in ROS baseline levels compared to N-iPSC-derived cardiomyocytes. Additionally, high glucose concentrations increased oxidative stress-induced ROS production compared to lower glucose conditions in both cell lines. Our preliminary data shows that high glucose generates excessive ROS and hyperpolarizes the mitochondrial membrane and may contribute to the inefficiency of diabetic and/or hyperglycemic individuals to be anesthetically preconditioned. By utilizing human iPSC-derived cardiomyocytes we can begin to understand the inability of hyperglycemic and diabetic individuals to be anesthetically preconditioned.

Cytotoxic effects of cisplatin, cis-dichlorodiammineplatinum(II), on Tetrahymena

1988 ◽  
Vol 90 (4) ◽  
pp. 707-716
Author(s):  
J.R. Nilsson
Keyword(s):  
Mitochondrial Membrane ◽  
Prolonged Treatment ◽  
Dependent Manner ◽  
Inner Mitochondrial Membrane ◽  
Cell Organelles ◽  
Cell Content ◽  
Cytotoxic Effects ◽  
Dense Granules ◽  
High Concentrations ◽  
Dose Dependent

A study was made of the effects of cisplatin, cis-dichlorodiammineplatinum(II) (5–250 mg l-1), on the physiology and fine structure of Tetrahymena. The physiological effects observed were dose-dependent. Endocytosis was inhibited reversibly in all, but late in the high, concentrations. After an initial dose-related increase, due to division of cells most advanced in the cell cycle, proliferation ceased for at least two normal cell generations (6 h) in 50 and 100 mg drug l-1, but for 24 h in 250 mg l-1, after which multiplication was resumed in a dose-dependent manner. Exposure to cisplatin resulted in the appearance of small, refractive granules and platinum (i.e. electron-dense material) accumulated in these granules. Fine structural observations of cells exposed to 250 mg drug l-1 showed nucleolar fusion and appearance initially of lipid droplets, dense granules and autophagosomes. A time-dependent redistribution of cell organelles was revealed by morphometry; in particular, the mitochondria increased in number, but decreased in size. Moreover, after prolonged treatment (24 h) and without cell division, the inner mitochondrial membrane had diminished and the ratio of the inner to the outer mitochondrial membrane was only half of the value for control mitochondria. Concomitantly with this decrease, the cell content of ATP was reduced to a similar extent. The findings indicate a specific action of cisplatin on mitochondria, resembling that induced in Tetrahymena by chloramphenicol and methotrexate.

Encircling granulosa cells protects against di-(2-ethylhexyl)phthalate-induced apoptosis in rat oocytes cultured in vitro

Zygote ◽  
2019 ◽  
Vol 27 (4) ◽  
pp. 203-213 ◽  
Author(s):  
Anima Tripathi ◽  
Vivek Pandey ◽  
A.N. Sahu ◽  
Alok K. Singh ◽  
Pawan K. Dubey
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Granulosa Cells ◽  
Mitochondrial Membrane ◽  
Dependent Manner ◽  
Apoptotic Markers ◽  
Induced Apoptosis ◽  
Ethylhexyl Phthalate

SummaryThe present study investigated if the presence of encircling granulosa cells protected against di(2-ethylhexyl)phthalate (DEHP)-induced oxidative stress in rat oocytes cultured in vitro. Denuded oocytes and cumulus–oocyte complexes (COCs) were treated with or without various doses of DEHP (0.0, 25.0, 50.0, 100, 200, 400 and 800 μM) in vitro. Morphological apoptotic changes, levels of oxidative stress and reactive oxygen species (ROS), mitochondrial membrane potential, and expression levels of apoptotic markers (Bcl2, Bax, cytochrome c) were analyzed. Our results showed that DEHP induced morphological apoptotic changes in a dose-dependent manner in denuded oocytes cultured in vitro. The effective dose of DEHP (400 µg) significantly (P>0.05) increased oxidative stress by elevating ROS levels and the mitochondrial membrane potential with higher mRNA expression and protein levels of apoptotic markers (Bax, cytochrome c). Encircling granulosa cells protected oocytes from DEHP-induced morphological changes, increased oxidative stress and ROS levels, as well as increased expression of apoptotic markers. Taken together our data suggested that encircling granulosa cells protected oocytes against DEHP-induced apoptosis and that the presence of granulosa cells could act positively towards the survival of oocytes under in vitro culture conditions and may be helpful during assisted reproductive technique programmes.

scholarly journals β-Lapachone Induces Acute Oxidative Stress in Rat Primary Astrocyte Cultures that is Terminated by the NQO1-Inhibitor Dicoumarol

2020 ◽  
Vol 45 (10) ◽  
pp. 2442-2455
Author(s):  
Johann Steinmeier ◽  
Sophie Kube ◽  
Gabriele Karger ◽  
Eric Ehrke ◽  
Ralf Dringen
Keyword(s):  
Oxidative Stress ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Glutathione Disulfide ◽  
Cellular Accumulation ◽  
Primary Astrocyte ◽  
Cultured Astrocytes ◽  
Rat Astrocytes ◽  
Quinone Acceptor ◽  
And Oxidative Stress

Abstract β-lapachone (β-lap) is reduced in tumor cells by the enzyme NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1) to a labile hydroquinone which spontaneously reoxidises to β-lap, thereby generating reactive oxygen species (ROS) and oxidative stress. To test for the consequences of an acute exposure of brain cells to β-lap, cultured primary rat astrocytes were incubated with β-lap for up to 4 h. The presence of β-lap in concentrations of up to 10 µM had no detectable adverse consequences, while higher concentrations of β-lap compromised the cell viability and the metabolism of astrocytes in a concentration- and time-dependent manner with half-maximal effects observed for around 15 µM β-lap after a 4 h incubation. Exposure of astrocytes to β-lap caused already within 5 min a severe increase in the cellular production of ROS as well as a rapid oxidation of glutathione (GSH) to glutathione disulfide (GSSG). The transient cellular accumulation of GSSG was followed by GSSG export. The β-lap-induced ROS production and GSSG accumulation were completely prevented in the presence of the NQO1 inhibitor dicoumarol. In addition, application of dicoumarol to β-lap-exposed astrocytes caused rapid regeneration of the normal high cellular GSH to GSSG ratio. These results demonstrate that application of β-lap to cultured astrocytes causes acute oxidative stress that depends on the activity of NQO1. The sequential application of β-lap and dicoumarol to rapidly induce and terminate oxidative stress, respectively, is a suitable experimental paradigm to study consequences of a defined period of acute oxidative stress in NQO1-expressing cells.

72 Protective Effects of C-Phycocyanin on the Developmental Competence of Porcine Parthenotes

2018 ◽  
Vol 30 (1) ◽  
pp. 174
Author(s):  
Y.-J. Niu ◽  
N.-H. Kim ◽  
X.-S. Cui
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane ◽  
Developmental Competence ◽  
Oxygen Species ◽  
Blastocyst Formation

C-Phycocyanin (CP) is a biliprotein enriched in blue-green algae that is known to possess antioxidant, anti-apoptosis, anti-inflammatory, and radical-scavenging properties in somatic cells. However, the protective effect of CP on porcine embryo developmental competence in vitro remains unclear. In the present study, we investigated the effect of CP on the development of porcine early embryos as well as its underlying mechanisms exposing them to H2O2 to induce oxidative stress. The levels of reactive oxygen species, mitochondrial membrane potential, apoptosis, DNA damage, and autophagy in the blastocysts were observed by staining with 2′,7′-dichlorodihydrofluorescein diacetate (H2DCF-DA), 5,5′,6,6’-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1), terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate (dUTP) nick-end labelling (TUNEL), anti-cytochrome c, and anti-γH2A.X (Ser139), respectively. Colocalization assay of mitochondria and cytochrome c of blastocysts were staining with MitoTracker Red CMXRos and anti-cytochrome c. All data were subjected to one-way ANOVA. Different concentrations of CP (1, 2, 5, 8, 10 µg mL−1) were added to porcine zygote medium 5 (PZM-5, l-glutamine concentration of PZM-3 was modified from 1 to 2 mM) during in vitro culture. The results showed that 5 µg mL−1 CP significantly increased blastocyst formation (62.5 ± 2.1 v. 52.7 ± 2.4; P < 0.05) and hatching rate (10.9 ± 1.9 v. 36.6 ± 5.2; P < 0.05) compared with controls. Blastocyst formation (53.1 ± 2.3 v. 40.1 ± 2.3; P < 0.05) and quality were significantly increased in the 50 µM H2O2 treatment group following 5 µg mL−1 CP addition. C-Phycocyanin prevented the H2O2-induced compromise of mitochondrial membrane potential, release of cytochrome c from the mitochondria, and generation of reactive oxygen species. Furthermore, apoptosis, DNA damage level, and autophagy in the blastocysts were attenuated by supplementation of CP in the H2O2-induced oxidative injury group compared with that in controls. These results suggest that CP has beneficial effects on the development of porcine parthenotes by attenuating mitochondrial dysfunction and oxidative stress.

Supplementation of kaempferol to in vitro maturation medium regulates oxidative stress and enhances subsequent embryonic development in vitro

Zygote ◽  
2019 ◽  
Vol 28 (1) ◽  
pp. 59-64
Author(s):  
Yuhan Zhao ◽  
Yongnan Xu ◽  
Yinghua Li ◽  
Qingguo Jin ◽  
Jingyu Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Treated Group ◽  
Control Group ◽  
Oxygen Species

SummaryKaempferol (KAE) is one of the most common dietary flavonols possessing biological activities such as anticancer, anti-inflammatory and antioxidant effects. Although previous studies have reported the biological activity of KAE on a variety of cells, it is not clear whether KAE plays a similar role in oocyte and embryo in vitro culture systems. This study investigated the effect of KAE addition to in vitro maturation on the antioxidant capacity of embryos in porcine oocytes after parthenogenetic activation. The effects of kaempferol on oocyte quality in porcine oocytes were studied based on the expression of related genes, reactive oxygen species, glutathione and mitochondrial membrane potential as criteria. The rate of blastocyst formation was significantly higher in oocytes treated with 0.1 µm KAE than in control oocytes. The mRNA level of the apoptosis-related gene Caspase-3 was significantly lower in the blastocysts derived from KAE-treated oocytes than in the control group and the mRNA expression of the embryo development-related genes COX2 and SOX2 was significantly increased in the KAE-treated group compared with that in the control group. Furthermore, the level of intracellular reactive oxygen species was significantly decreased and that of glutathione was significantly increased after KAE treatment. Mitochondrial membrane potential (ΔΨm) was increased and the activity of Caspase-3 was significantly decreased in the KAE-treated group compared with that in the control group. Taken together, these results suggested that KAE is beneficial for the improvement of embryo development by inhibiting oxidative stress in porcine oocytes.

scholarly journals ANG II promotes autophagy in podocytes

2010 ◽  
Vol 299 (2) ◽  
pp. C488-C496 ◽  
Author(s):  
Anju Yadav ◽  
Sridevi Vallabu ◽  
Shitij Arora ◽  
Pranay Tandon ◽  
Divya Slahan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ang Ii ◽  
Electron Microscopic ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Microscopic Studies ◽  
Autophagic Process

Podocytes are an integral and important constituent of the glomerular filtration barrier (GFB) and are exposed to a higher concentrations of ANG II in diseased states; consequently, podocytes may accumulate oxidized proteins and damaged mitochondria. In the present study, we evaluated the effect of ANG II on the podocyte autophagic process, which is likely to be triggered in order to degrade unwanted proteins and damaged organelles. To quantitate the occurrence of autophagy, electron microscopic studies were carried out on control and ANG II-treated conditionally immortalized mouse podocytes (CIMPs). ANG II-treated cells showed a fivefold greater number of autophagosomes/field compared with control cells. This proautophagic effect of ANG II was inhibited by pretreatment with 3-methyladenine, an inhibitor of autophagy. ANG II also enhanced podocyte expression of autophagic genes such as LC3-2 and beclin-1. Since oxidative stress is often associated with the induction of autophagy, we examined the effect of ANG II on podocyte reactive oxygen species (ROS) generation. ANG II enhanced podocyte ROS generation in a time-dependent manner. To determine whether there is a causal relationship between ANG II-induced oxidative stress and induction of autophagy, we evaluated the effect of antioxidants on ANG II-induced autophagy. As expected, the proautophagic effect of ANG II was inhibited by antioxidants. We conclude that ANG II promotes podocyte autophagy through the generation of ROS.

scholarly journals The maturation of the inner membrane of foetal rat liver mitochondria. An example of a positive-feedback mechanism

1975 ◽  
Vol 150 (3) ◽  
pp. 477-488 ◽  
Author(s):  
J K Pollak
Keyword(s):  
Oxidative Phosphorylation ◽  
Rat Liver ◽  
Mitochondrial Membrane ◽  
Respiratory Control ◽  
Liver Mitochondria ◽  
Neonatal Rat ◽  
Rat Liver Mitochondria ◽  
Inner Mitochondrial Membrane ◽  
Mature Adult ◽  
Foetal Rat

A new method was devised for the isolation of foetal and neonatal rat lvier mitochondria, giving higher yields than conventional methods. 2. During development from the perinatal period to the mature adult, the ratio of cytochrome oxidase/succinate-cytochrome c reductase changes. 3. The inner mitochondrial membrane of foetal liver mitochondria possesses virtually no osmotic activity; the permeability to sucrose decreases with increasing developmental age. 4. Foetal rat liver mitochondria possess only marginal respiratory control and do not maintain Ca2+-induced respiration; they also swell in respiratory-control medium in the absence of substrate. ATP enhances respiratory control and prevents swelling, adenylyl imidodiphosphate, ATP+atractyloside enhance the R.C.I. (respiratory control index), Ca2+-induced respiratory control and prevent swelling, whereas GTP and low concentrations of ADP have none of these actions. It is concluded that the effect of ATP depends on steric interaction with the inner mitochondrial membrane. 5. When 1-day pre-partum foetuses are obtained by Caesarean section and maintained in a Humidicrib for 90 min, mitochondrial maturation is ‘triggered’, so that their R.C.I. is enhanced and no ATP is required to support Ca2+-dependent respiratory control or to inhibit mitochondrial swelling. 6. It is concluded that foetal rat liver mitochondria in utero do not respire, although they are capable of oxidative phosphorylation in spite of their low R.C.I. The different environmental conditions which the neonatal rat encounters ex utero enable the hepatic mitochondria to produce ATP, which interacts with the inner mitochondrial membrane to enhance oxidative phosphorylation by an autocatalytic mechanism.

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