On the oxidative damage by cadmium to kidney mitochondrial functions

2019 ◽  
Vol 97 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Natalia Pavón ◽  
Mabel Buelna-Chontal ◽  
Arturo Macías-López ◽  
Francisco Correa ◽  
Cristina Uribe-Álvarez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heavy Metals ◽  
Mitochondrial Dna ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Functions ◽  
Electrical Gradient ◽  
Radical Generation ◽  
Parameters Of Interest ◽  
Stimulation Of

In the kidney, the accumulation of heavy metals such as Cd2+ produces mitochondrial dysfunctions, i.e., uncoupling of the oxidative phosphorylation, inhibition of the electron transport through the respiratory chain, and collapse of the transmembrane electrical gradient. This derangement may be due to the fact that Cd2+ induces the transition of membrane permeability from selective to nonselective via the opening of a transmembrane pore. In fact, Cd2+ produces this injury through the stimulation of oxygen-derived radical generation, inducing oxidative stress. Several molecules have been used to avoid or even reverse Cd2+-induced mitochondrial injury, for instance, cyclosporin A, resveratrol, dithiocarbamates, and even EDTA. The aim of this study was to explore the possibility that the antioxidant tamoxifen could protect mitochondria from the deleterious effects of Cd2+. Our results indicate that the addition of 1 μmol/L Cd2+ to mitochondria collapsed the transmembrane electrical gradient, induced the release of cytochrome c, and increased both the generation of H2O2 and the oxidative damage to mitochondrial DNA (among other measured parameters). Of interest, these mitochondrial dysfunctions were ameliorated after the addition of tamoxifen.

scholarly journals 57 Carnosine prevents oxidative damage in myoblast cells derived from porcine skeletal muscle

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 59-59
Author(s):  
Marie-France Palin ◽  
Jérôme Lapointe ◽  
Claude Gariépy ◽  
Danièle Beaudry ◽  
Claudia Kalbe
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Metal Ion ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Biochemical Properties ◽  
Antioxidant Enzyme Activities ◽  
Antioxidant Genes ◽  
Mitochondrial Functions ◽  
Myoblast Cells

Abstract Carnosine (β-alanyl-L-histidine) is a molecule naturally and exclusively present in muscle food with the highest concentrations found in skeletal muscles and brain of the animal. Among its numerous biochemical properties, carnosine has antioxidant activity which include metal ion chelation and free radical scavenging. We have recently reported that high muscle carnosine content in pig is associated with better meat quality. Moreover, supplementing pigs with β-alanine reduced oxidative damage to Longissimus muscle (LM) lipids and proteins. Among previously reported antioxidant activities, carnosine was found to limit the production of reactive oxygen species (ROS) and increase antioxidant enzyme activities. However, these studies were mainly conducted in rodents and cell lines and mechanisms in play remain to be characterized. To determine the effect of carnosine in preventing oxidative damage and characterize the mechanisms in play, we have undertaken experiments using the progeny (myoblasts) of satellite cells isolated from the LM of newborn piglets. Cells were treated with carnosine (0, 10, 25 and 50 mM) for 48 h and were then either collected immediately or treated with H2O2 (0.3 mM, 1 h) to induce an oxidative stress. Our results showed that carnosine prevents oxidative stress through the reduction of total intracellular ROS and by modulating the antioxidant system in myoblasts.Carnosine increased the mRNA abundance of NEF2L2, a transcription factor activated by oxidative stress, and several of its downstream regulated antioxidant genes. Western blot analyses further suggest that the protective effect of carnosine on H2O2-induced oxidative stress is mediated through the p38 MAPK intracellular pathway. Finally, the addition of carnosine to H2O2-treated myoblasts increased the basal cellular oxygen consumption rate (OCR), the ATP-linked OCR and proton leaks, thus suggesting an effect of carnosine on mitochondrial functions. Taken together, these findings demonstrate the important role of carnosine in preventing oxidative damage in porcine muscle cells.

Oxidative Stress, Mitochondrial DNA Mutation, and Impairment of Antioxidant Enzymes in Aging

2002 ◽  
Vol 227 (9) ◽  
pp. 671-682 ◽  
Author(s):  
Yau-Huei Wei ◽  
Hsin-Chen Lee
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Antioxidant Enzymes ◽  
Oxidative Damage ◽  
Large Scale ◽  
Wide Spectrum ◽  
Radical Scavenging ◽  
Mtdna Mutations ◽  
Enhanced Production ◽  
Age Related

Mitochondria do not only produce less ATP, but they also increase the production of reactive oxygen species (ROS) as byproducts of aerobic metabolism in the aging tissues of the human and animals. It is now generally accepted that aging-associated respiratory function decline can result in enhanced production of ROS in mitochondria. Moreover, the activities of free radical-scavenging enzymes are altered in the aging process. The concurrent age-related changes of these two systems result in the elevation of oxidative stress in aging tissues. Within a certain concentration range, ROS may induce stress response of the cells by altering expression of respiratory genes to uphold the energy metabolism to rescue the cell. However, beyond the threshold, ROS may cause a wide spectrum of oxidative damage to various cellular components to result in cell death or elicit apoptosis by induction of mitochondrial membrane permeability transition and release of apoptogenic factors such as cytochrome c. Moreover, oxidative damage and large-scale deletion and duplication of mitochondrial DNA (mtDNA) have been found to increase with age in various tissues of the human. Mitochondria act like a biosensor of oxidative stress and they enable cell to undergo changes in aging and age-related diseases. On the other hand, it has recently been demonstrated that impairment in mitochondrial respiration and oxidative phosphorylation elicits an increase in oxidative stress and causes a host of mtDNA rearrangements and deletions. Here, we review work done in the past few years to support our view that oxidative stress and oxidative damage are a result of concurrent accumulation of mtDNA mutations and defective antioxidant enzymes in human aging.

scholarly journals Oxidative Stress Induces Mitochondrial Compromise in CD4 T Cells From Chronically HCV-Infected Individuals

2021 ◽  
Vol 12 ◽  
Author(s):  
Madison Schank ◽  
Juan Zhao ◽  
Ling Wang ◽  
Lam Ngoc Thao Nguyen ◽  
Dechao Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Mitochondrial Dna ◽  
Cd4 T Cells ◽  
Hcv Infection ◽  
Cellular Respiration ◽  
Peroxisome Proliferator ◽  
Mtdna Copy Number ◽  
Mitochondrial Mass ◽  
Mitochondrial Functions

We have previously shown that chronic Hepatitis C virus (HCV) infection can induce DNA damage and immune dysfunctions with excessive oxidative stress in T cells. Furthermore, evidence suggests that HCV contributes to increased susceptibility to metabolic disorders. However, the underlying mechanisms by which HCV infection impairs cellular metabolism in CD4 T cells remain unclear. In this study, we evaluated mitochondrial mass and intracellular and mitochondrial reactive oxygen species (ROS) production by flow cytometry, mitochondrial DNA (mtDNA) content by real-time qPCR, cellular respiration by seahorse analyzer, and dysregulated mitochondrial-localized proteins by Liquid Chromatography-Mass Spectrometry (LC-MS) in CD4 T cells from chronic HCV-infected individuals and health subjects. Mitochondrial mass was decreased while intracellular and mitochondrial ROS were increased, expressions of master mitochondrial regulators peroxisome proliferator-activated receptor 1 alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) were down-regulated, and oxidative stress was increased while mitochondrial DNA copy numbers were reduced. Importantly, CRISPR/Cas9-mediated knockdown of mtTFA impaired cellular respiration and reduced mtDNA copy number. Furthermore, proteins responsible for mediating oxidative stress, apoptosis, and mtDNA maintenance were significantly altered in HCV-CD4 T cells. These results indicate that mitochondrial functions are compromised in HCV-CD4 T cells, likely via the deregulation of several mitochondrial regulatory proteins.

scholarly journals Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

2015 ◽  
Vol 119 (2) ◽  
pp. 148-156 ◽  
Author(s):  
Márcia F. da Silva ◽  
Antônio J. Natali ◽  
Edson da Silva ◽  
Gilton J. Gomes ◽  
Bruno G. Teodoro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Therapy ◽  
Diabetic Rat ◽  
Swimming Training ◽  
Mitochondrial Dysfunctions ◽  
Mptp Opening ◽  
Rat Hearts ◽  
Mitochondrial Functions ◽  
Insulin Replacement ◽  
And Mitochondrial Functions

We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca2+]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca2+]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca2+]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca2+ uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca2+]i transient, UCP-2 expression, and mitochondrial Ca2+ uptake. Insulin replacement further normalized [Ca2+]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca2+ disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts.

scholarly journals Mitophagy could fight Parkinson’s disease through antioxidant action

2019 ◽  
Vol 30 (7) ◽  
pp. 729-742 ◽  
Author(s):  
Anthea Di Rita ◽  
Flavie Strappazzon
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lysosomal Degradation ◽  
Functional Connection ◽  
Mitochondrial Dysfunctions ◽  
Stress Oxidative ◽  
And Oxidative Stress ◽  
Stimulation Of

Abstract During aging, the process of mitophagy, a system that allows the removal of dysfunctional mitochondria through lysosomal degradation, starts to malfunction. Because of this defect, damaged mitochondria are not removed correctly, and their decomposing components accumulate inside the cells. Dysfunctional mitochondria that are not removed by mitophagy produce high amounts of reactive oxygen species (ROS) and, thus, cause oxidative stress. Oxidative stress, in turn, is very harmful for the cells, neuronal cells, in particular. Consequently, the process of mitophagy plays a crucial role in mitochondria-related disease. Mitochondrial dysfunctions and oxidative stress are well-established factors contributing to Parkinson’s disease (PD), one of the most common neurodegenerative disorders. In this review, we report various known antioxidants for PD treatments and describe the stimulation of mitophagy process as a novel and exciting method for reducing oxidative stress in PD patients. We describe the different mechanisms responsible for mitochondria removal through the mitophagy process. In addition, we review the functional connection between mitophagy induction and reduction of oxidative stress in several in vitro models of PD and also agents (drugs and natural compounds) already known to be antioxidants and to be able to activate mitophagy. Finally, we propose that there is an urgent need to test the use of mitophagy-inducing antioxidants in order to fight PD.

scholarly journals Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 220
Author(s):  
Csaba Szabo
Keyword(s):  
Dna Repair ◽  
Mitochondrial Dna ◽  
Hydrogen Sulfide ◽  
Cancer Cells ◽  
Mitochondrial Fission ◽  
Cytotoxic Action ◽  
Atp Production ◽  
Mitochondrial Functions ◽  
Mitochondrial Dna Repair ◽  
Stimulation Of

Hydrogen sulfide (H2S) has a long history as toxic gas and environmental hazard; inhibition of cytochrome c oxidase (mitochondrial Complex IV) is viewed as a primary mode of its cytotoxic action. However, studies conducted over the last two decades unveiled multiple biological regulatory roles of H2S as an endogenously produced mammalian gaseous transmitter. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST) are currently viewed as the principal mammalian H2S-generating enzymes. In contrast to its inhibitory (toxicological) mitochondrial effects, at lower (physiological) concentrations, H2S serves as a stimulator of electron transport in mammalian mitochondria, by acting as an electron donor—with sulfide:quinone oxidoreductase (SQR) being the immediate electron acceptor. The mitochondrial roles of H2S are significant in various cancer cells, many of which exhibit high expression and partial mitochondrial localization of various H2S producing enzymes. In addition to the stimulation of mitochondrial ATP production, the roles of endogenous H2S in cancer cells include the maintenance of mitochondrial organization (protection against mitochondrial fission) and the maintenance of mitochondrial DNA repair (via the stimulation of the assembly of mitochondrial DNA repair complexes). The current article overviews the state-of-the-art knowledge regarding the mitochondrial functions of endogenously produced H2S in cancer cells.

Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins

2006 ◽  
Vol 20 (8) ◽  
pp. 1064-1073 ◽  
Author(s):  
Alberto Sanz ◽  
Pilar Caro ◽  
Victoria Ayala ◽  
Manuel Portero-Otin ◽  
Reinald Pamplona ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Oxidative Damage ◽  
Oxygen Radical ◽  
Methionine Restriction ◽  
Radical Generation

Study of Uncoupling Protein 2 (UCP2) Function during Erythroid Differentiation and Maturation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3535-3535
Author(s):  
Alvaro A. Elorza ◽  
Sarah E. Haigh ◽  
Hanna K. Mikkola ◽  
Orian S. Shirihai
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Peripheral Blood ◽  
Biosynthetic Pathway ◽  
Erythroid Differentiation ◽  
Heme Biosynthesis ◽  
Erythroid Cell ◽  
Primary Mouse ◽  
Wide Range ◽  
Stimulation Of

Abstract Mitochondrial oxidative stress is thought to play a key role in sideroblastic anemia and the myelodysplastic syndrome. Potential sources of reactive radicals reside in the heme biosynthetic pathway involving the import and production of pro-oxidant agents, such as ALA and iron and in the respiratory chain. Antioxidant mechanisms are, therefore, expected to be an integral function in erythroid differentiation and their impairment is expected to affect hemoglobinization and maturation. The mitochondrial uncoupling proteins have been shown to reduce oxidative stress through the generation of proton leak across the inner membrane of the mitochondria. They have been implicated in a wide range of physiological and pathological states, including obesity, diabetes, aging neurodegenerative, and immunological diseases. Here we report that UCP2 is induced during erythroid differentiation and that UCP2 deficient mice have a delayed recovery from anemia. We hypothesized that erythroid heme biosynthesis is accompanied by oxidative stress, which results in the induction of UCP2, and that UCP2 plays a role in erythroid maturation by preventing oxidative stress and damage. We found that UCP2 transcripts and protein are induced following the activation of GATA-1 in G1ER cells and during DMSO, butyrate and heme -induced differentiation of murine erythroleukemic (MEL) and K652 erythroid cell lines. Similarly, differentiation of primary mouse c-kit+ / Ter119− erythroid progenitors to Ter119+ is accompanied by induction of UCP2 transcripts. To test the functional significance of UCP2 in erythroid differentiation we studied a UCP2 null mouse. Peripheral blood analysis from UCP2 KO mice revealed a mild elevation of the reticulocyte index as compared to wild type (WT C57BL/6J) mice, which may be related to mild anemia. To test the role of UCP2 in recovery from anemia, we treated WT and UCP2 KO mice with phenylhydrazine for 3 days and studied erythropoiesis using FACS analysis of Ter119 and CD71 surface markers in cells isolated from bone marrow. Stimulation of erythropoiesis was more rapid in the WT mice as compared to the UCP2 KO. The delay in the mutant is more pronounced at the stage of the proerythroblast and is also reflected in the peripheral blood where a higher level of reticulocytes was transiently observed. By 9 days the UCP2 KO mice peripheral blood count was identical to the WT. Analysis of oxidative damage confirmed that UCP2 acts to reduce oxidative damage of mitochondrial proteins. The delayed reticulocytosis could not however be explained by cell death or by reduced hemoglobinization. The increased oxidative damage present in the UCP2 null cells during erythroid differentiation and maturation did not result in the stimulation of apoptosis as revealed by identical Annexin V staining profile of UCP2 KO and WT mice. Remarkably, iron incorporation and hemoglobin content assays ruled out a function of UCP2 in the process of heme biosynthesis per-se. We therefore conclude that UCP2 deficiency regulates maturation in the erythroid lineage independent of the heme biosynthetic pathway.

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