scholarly journals Mitochondrial respiratory chain and thioredoxin reductase regulate intermembrane Cu,Zn-superoxide dismutase activity: implications for mitochondrial energy metabolism and apoptosis

2007 ◽  
Vol 405 (1) ◽  
pp. 173-179 ◽  
Author(s):  
Pedro Iñarrea ◽  
Hadi Moini ◽  
Derick Han ◽  
Daniel Rettori ◽  
Ignacio Aguiló ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Thioredoxin Reductase ◽  
Oxidative Modification ◽  
Rat Liver Mitochondria ◽  
Intermembrane Space ◽  
Cytochrome C Release ◽  
Mitochondrial Energy Metabolism ◽  
Mitochondrial Functions ◽  
The Impact ◽  
Exogenous H2o2

IMS (intermembrane space) SOD1 (Cu/Zn-superoxide dismutase) is inactive in isolated intact rat liver mitochondria and is activated following oxidative modification of its critical thiol groups. The present study aimed to identify biochemical pathways implicated in the regulation of IMS SOD1 activity and to assess the impact of its functional state on key mitochondrial events. Exogenous H2O2 (5 μM) activated SOD1 in intact mitochondria. However, neither H2O2 alone nor H2O2 in the presence of mitochondrial peroxiredoxin III activated SOD1, which was purified from mitochondria and subsequently reduced by dithiothreitol to an inactive state. The reduced enzyme was activated following incubation with the superoxide generating system, xanthine and xanthine oxidase. In intact mitochondria, the extent and duration of SOD1 activation was inversely correlated with mitochondrial superoxide production. The presence of TxrR-1 (thioredoxin reductase-1) was demonstrated in the mitochondrial IMS by Western blotting. Inhibitors of TxrR-1, CDNB (1-chloro-2,4-dinitrobenzene) or auranofin, prolonged the duration of H2O2-induced SOD1 activity in intact mitochondria. TxrR-1 inactivated SOD1 purified from mitochondria in an active oxidized state. Activation of IMS SOD1 by exogenous H2O2 delayed CaCl2-induced loss of transmembrane potential, decreased cytochrome c release and markedly prevented superoxide-induced loss of aconitase activity in intact mitochondria respiring at state-3. These findings suggest that H2O2, superoxide and TxrR-1 regulate IMS SOD1 activity reversibly, and that the active enzyme is implicated in protecting vital mitochondrial functions.

scholarly journals Redox activation of mitochondrial intermembrane space Cu,Zn-superoxide dismutase

2005 ◽  
Vol 387 (1) ◽  
pp. 203-209 ◽  
Author(s):  
Pedro IÑARREA ◽  
Hadi MOINI ◽  
Daniel RETTORI ◽  
Derick HAN ◽  
Jesús MARTÍNEZ ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Outer Membrane ◽  
Alkylating Agents ◽  
Liver Mitochondria ◽  
Oxidative Modification ◽  
Mitochondrial Outer Membrane ◽  
Rat Liver Mitochondria ◽  
Intermembrane Space ◽  
H2o2 Treatment ◽  
Mitochondrial Intermembrane Space

The localization of Cu,Zn-superoxide dismutase in the mitochondrial intermembrane space suggests a functional relationship with superoxide anion (O2•−) released into this compartment. The present study was aimed at examining the functionality of Cu,Zn-superoxide dismutase and elucidating the molecular basis for its activation in the intermembrane space. Intact rat liver mitochondria neither scavenged nor dismutated externally generated O2•−, unless the mitochondrial outer membrane was disrupted selectively by digitonin. The activation of the intermembrane space Cu,Zn-superoxide dismutase following the disruption of mitochondrial outer membrane was largely inhibited by bacitracin, an inhibitor of protein disulphide-isomerase. Thiol alkylating agents, such as N-methylmaleimide or iodoacetamide, decreased intermembrane space Cu,Zn-superoxide dismutase activation during, but not after, disruption of the outer membrane. This inhibitory effect was overcome by exposing mitochondria to low micromolar concentrations of H2O2 before disruption of the outer membrane in the presence of the alkylating agents. Moreover, H2O2 treatment alone enabled intact mitochondria to scavenge externally generated O2•−. These findings suggest that intermembrane space Cu,Zn-superoxide dismutase is inactive in intact mitochondria and that an oxidative modification of its critical thiol groups is necessary for its activation.

Ceramide induces cytochrome c release from isolated mitochondria

1999 ◽  
Vol 66 ◽  
pp. 27-31 ◽  
Author(s):  
Christoph Richter ◽  
Pedram Ghafourifar
Keyword(s):  
Cytochrome C ◽  
Membrane Integrity ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Cytochrome C Release ◽  
Mitochondrial Oxygen Consumption ◽  
Mitochondrial Functions ◽  
Cyt C ◽  
C6 Ceramide

This chapter addresses the role of mitochondria in apoptosis. Emphasis is put on the recently observed influence of ceramides on mitochondrial functions. We report here that N-acetylsphingosine (C2-ceramide), N-hexanoylsphingosine (C6-ceramide) and, to a much lesser extent, C2-dihydroceramide, induce cytochrome c (cyt c) release from isolated rat liver mitochondria. Ceramide-induced cyt c release is prevented by a low concentration of Bcl-2. The release takes place when cyt c is oxidized, but not when it is reduced. Upon cyt c release mitochondrial oxygen consumption, mitochondrial transmembrane potential (ΔΨm) and Ca2+ retention are diminished. Bcl-2 prevents, and addition of cyt c reverses, the alteration of these mitochondrial functions. In ATP-energized mitochondria ceramides do not alter ΔΨm, neither when cyt c is oxidized nor when it is reduced. This rules out a non-specific disturbance by ceramides of mitochondrial-membrane integrity. It is concluded that some of the apoptogenic properties of ceramides are mediated via their interaction with mitochondrial cyt c followed by its release.

Distribution of protein disulphide isomerase in rat liver mitochondria

2001 ◽  
Vol 356 (2) ◽  
pp. 567-570 ◽  
Author(s):  
Maria Pia RIGOBELLO ◽  
Arianna DONELLA-DEANA ◽  
Luca CESARO ◽  
Alberto BINDOLI
Keyword(s):  
Thioredoxin Reductase ◽  
Immunoblot Analysis ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Specific Marker ◽  
Protein Disulphide Isomerase ◽  
Mitochondrial Functions ◽  
The Matrix ◽  
Molecular Masses

Here we report the localization of protein disulphide isomerase (PDI) in the mitochondrial compartments, comparing it with that of thioredoxin reductase. The latter enzyme is present mostly in the matrix, whereas PDI is located at the level of the outer membrane. We characterize the different submitochondrial fractions with specific marker enzymes. PDI, whether isolated from whole mitochondria or from purified outer membranes, exhibits the same electrophoretic mobility, indicating identical molecular masses. Moreover, immunoblot analysis with monoclonal anti-PDI antibody shows immunoreactivity only with the microsomal PDI, indicating the specificity of the mitochondrial isoform. The significance of these findings is discussed with reference to the potential role of PDI and thioredoxin reductase in regulating the mitochondrial functions dependent on the thiol–disulphide transition.

Assessment of Superoxide Dismutase and Catalase Evolution in Different Stages of an Experimental Endometriosis

2017 ◽  
Vol 68 (6) ◽  
pp. 1381-1383
Author(s):  
Allia Sindilar ◽  
Carmen Lacramioara Zamfir ◽  
Eusebiu Viorel Sindilar ◽  
Alin Constantin Pinzariu ◽  
Eduard Crauciuc ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Reproductive Function ◽  
Female Rats ◽  
Oxygen Species ◽  
Efficient Treatment ◽  
Endometrial Cells ◽  
Gynecological Disorder ◽  
The Impact

Endometriosis is described as a gynecological disorder characterized by the presence of endometrial tissue outside the uterus; extensively explored because of its increasing incidency, with an indubitable diagnostic only after invasive surgery, with no efficient treatment, it has still many aspects to be elucidated. A growing body of facts sustain oxidative stress as a crucial factor between the numerous incriminated factors implicated in endometriosis ethiopathogeny. Reactive oxygen species(ROS) act to decline reproductive function. Our study intends to determine if an experimental model of endometriosis may be useful to assess the impact of oxidative stress on endometrial cells; we have used a murine model of 18 adult Wistar female rats. A fragment from their left uterine horn was implanted in the abdominal wall. After 4 weeks, a laparatomy was performed, 5 endometrial implants were removed, followed by biochemical tissue assay of superoxide dismutase(SOD) and catalase(CAT). At the end of the experiment, the rats were sacrificed, the implants were removed for histopathological exam and biochemical assay of antioxidant enzymes. The results revealed decreased levels of antioxidant enzymes, pointing on significant oxidative stress involvement.

P1, P5-Bis-(5′-adenosyl)pentaphosphate: Is this Adenylate Kinase Inhibitor Substrate for Mitochondrial Processes?

1977 ◽  
Vol 32 (9-10) ◽  
pp. 786-791 ◽  
Author(s):  
Josef Köhrle ◽  
Joachim Lüstorff ◽  
Eckhard Schlimme
Keyword(s):  
Adenylate Kinase ◽  
Kinase Inhibitor ◽  
Adenine Nucleotide ◽  
Nucleoside Diphosphate Kinase ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Rat Liver Mitochondria ◽  
Intermembrane Space ◽  
Rabbit Muscle ◽  
Inner Mitochondrial Membrane

Abstract 1. P1, P5-Bis-(5′-adenosyl)pentaphosphate (Ap5A) inhibits “soluble” adenylate kinase even when this enzyme is an integral part of the complete mitochondrion. The Ki is 10-5м , i. e. about two orders of magnitude higher than the inhibitor constants determined for the purified adenylate kinase of rabbit muscle and an enzyme preparation separated from the mitochondrial intermembrane space. The weaker inhibitory effect is due to a lower accessibility of the enzyme.2. As to be expected Ap5A which is of the “multisubstrate analogue”-type does not affect mito­ chondrial nucleoside diphosphate kinase.3. Though Ap5A owns the structural elements of both ATP and ADP it is not a substrate of the adenine nucleotide carrier, i.e. neither it is exchanged across the inner mitochondrial membrane nor specifically bound.4. Ap5A is not metabolized by rat liver mitochondria.

scholarly journals Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1625
Author(s):  
Theresa C. Sutherland ◽  
Arthur Sefiani ◽  
Darijana Horvat ◽  
Taylor E. Huntington ◽  
Yuanjiu Lei ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Traumatic Injury ◽  
Axon Growth ◽  
Neurite Growth ◽  
Growth Potential ◽  
Mitochondrial Functions ◽  
Cord Injury ◽  
Age Dependent ◽  
Mitochondria Functions ◽  
The Impact

The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

The Impact of Concomitant Chronic Pancreatitis on Prooxidant-antioxidant Status and Other Conditions in Osteoarthritis

2016 ◽  
pp. 75-78
Author(s):  
Liliia Babynets ◽  
Tetiana Maevska
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Chronic Pancreatitis ◽  
Functional Capacity ◽  
Antioxidant Status ◽  
Activation Parameters ◽  
Tissue Destruction ◽  
The Impact ◽  
Stress Accumulation

The study proved that patients with combined progress of osteoarthritis and chronic pancreatitis have reliable top-level activation of lipid peroxidation in terms of malonyc aldehyde and tissue destruction in terms of oxyproline, weakening of the antioxidant level (in terms of superoxide dismutase and SH-groups) and activation parameters of catalase and ceruloplasmin (p<0,05). The authentic predictority of patients biological age, duration of combined clinical courses, the functional capacity of the pancreas in terms of fecal α-elastase, structural state by ultrasound criteria for progression effects of oxidative stress, accumulation oxyproline activation parameters catalase and ceruloplasmin, which statistically was reflected by the presence of mainly moderate of significant correlations between these groups of indicators have been identified.

Abstract 34: Endogenous Superoxide Dismutase Protects From Impaired Generation of Activated Protein C and Enhanced Susceptibility to Experimental Thrombosis in Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Sanjana Dayal ◽  
Sean X Gu ◽  
Katinan M Wilson ◽  
Ryan Hutchins ◽  
Steven R Lentz
Keyword(s):  
Superoxide Dismutase ◽  
Protein C ◽  
Activated Protein C ◽  
Vena Cava ◽  
Oxidative Modification ◽  
Mrna Levels ◽  
Endothelial Protein C Receptor ◽  
Experimental Thrombosis

In vitro studies have suggested that reactive oxygen species such as superoxide can produce prothrombotic effects, including enhanced platelet activation, increased tissue factor (TF) expression, and an oxidative modification in thrombomodulin impairing its capacity to enhance the generation of activated protein C (APC) by thrombin. It is not known, however, if elevated levels of superoxide accelerate susceptibility to experimental thrombosis in vivo . We used mice genetically deficient in superoxide dismutase-1 (SOD1, an antioxidant enzyme that dismutates superoxide to hydrogen peroxide), to test the hypothesis that lack of SOD1 enhances susceptibility to thrombosis. Susceptibility to carotid artery thrombosis in a photochemical injury model demonstrated that Sod1-/- mice formed stable occlusions significantly faster than Sod1+/+ mice (P<0.05). In an inferior vena cava (IVC) stasis model Sod1- /- mice developed significantly larger thrombi 48 hours after IVC ligation (P<0.05 vs. Sod1+/+ mice). After activation with thrombin (0.5 U/ml) or convulxin (200 ng/ml), no differences in surface expression of P-selectin or binding of fibrinogen were observed between platelets from Sod1-/- and Sod1+/+ mice. The expression of TF mRNA in lung measured by real time qPCR showed similar levels in Sod1-/- and Sod1 +/+ mice. However, the activation of exogenous protein C by thrombin in lung homogenates was decreased in Sod1 -/- mice (P<0.05 vs. Sod1 +/+ mice). Further, in vivo generation of activated protein C in response to thrombin (40 U/Kg) infusion was significantly lower in Sod1-/- mice (P<0.05 vs. Sod1+/+ mice). No differences in mRNA levels for thrombomodulin or endothelial protein C receptor were detected in Sod1 -/- mice vs. Sod1 +/+ mice, suggesting that altered generation of activated protein C in Sod1-/- mice may be related to a direct oxidative effect on thrombomodulin. In accordance, thrombomodulin treated with xanthine/hypoxanthine showed 40% loss of ability to activate protein C that was overcome by addition of SOD and catalase (P<0.05). We conclude that endogenous SOD1 in mice protects from impaired generation of activated protein C and accelerated thrombosis.

scholarly journals Cytoprotective Effects of N-Acetylcysteine on Streptozotocin- Induced Oxidative Stress and Apoptosis in RIN-5F Pancreatic β-Cells

2018 ◽  
Vol 51 (1) ◽  
pp. 201-216 ◽  
Author(s):  
Arwa M.T. Al-Nahdi ◽  
Annie John ◽  
Haider  Raza
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Molecular Mechanisms ◽  
Protective Action ◽  
Mitochondrial Enzymes ◽  
Partial Recovery ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Mitochondrial Energy Metabolism ◽  
Mitochondrial Functions

Background/Aims: Numerous studies have reported overproduction of reactive oxygen species (ROS) and alterations in mitochondrial energy metabolism in the development of diabetes and its complications. The potential protective effects of N-acetylcysteine (NAC) in diabetes have been reported in many therapeutic studies. NAC has been shown to reduce oxidative stress and enhance redox potential in tissues protecting them against oxidative stress associated complications in diabetes. In the current study, we aimed to investigate the molecular mechanisms of the protective action of NAC on STZ-induced toxicity in insulin secreting Rin-5F pancreatic β-cells. Methods: Rin-5F cells were grown to 80% confluence and then treated with 10mM STZ for 24h in the presence or absence of 10mM NAC. After sub-cellular fractionation, oxidative stress, GSH-dependent metabolism and mitochondrial respiratory functions were studied using spectrophotometric, flow cytometric and Western blotting techniques. Results: Our results showed that STZ-induced oxidative stress and apoptosis caused inhibition in insulin secretion while NAC treatment restored the redox homeostasis, enhanced insulin secretion in control cells and prevented apoptosis in STZ-treated cells. Moreover, NAC attenuated the inhibition of mitochondrial functions induced by STZ through partial recovery of the mitochondrial enzymes and restoration of membrane potential. STZ-induced DNA damage and expression of apoptotic proteins were significantly inhibited in NAC-treated cells. Conclusion: Our results suggest that the cytoprotective action of NAC is mediated via suppression of oxidative stress and apoptosis and restoration of GSH homeostasis and mitochondrial bioenergetics. This study may, thus, help in better understanding the cellular defense mechanisms of pancreatic β-cells against STZ-induced cytotoxicity.

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