Mitochondrial [dys]function; culprit in pre-eclampsia?

2016 ◽  
Vol 130 (14) ◽  
pp. 1179-1184 ◽  
Author(s):  
Cathal Michael McCarthy ◽  
Louise Clare Kenny
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Mitochondrial Dysfunction ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Redox Signalling ◽  
Mitochondrial Superoxide ◽  
Mitochondrial Ros ◽  
Signalling Systems

Mitochondria are extensively identified for their bioenergetic capacities; however, recently these metabolic hubs are increasingly being appreciated as critical regulators of numerous cellular signalling systems. Mitochondrial reactive oxygen species have evolved as a mode of cross-talk between mitochondrial function and physiological systems, to sustain equipoise and foster adaption to cellular stress. Redox signalling mediated by exaggerated mitochondrial-ROS (reactive oxygen species) has been incriminated in a plethora of disease pathologies. Excessive production of mitochondrial ROS is intrinsically linked to mitochondrial dysfunction. Furthermore, mitochondrial dysfunction is a key facilitator of oxidative stress, inflammation, apoptosis and metabolism. These are key pathogenic intermediaries of pre-eclampsia, hence we hypothesize that mitochondrial dysfunction is a pathogenic mediator of oxidative stress in the pathophysiology of pre-eclampsia. We hypothesize that mitochondrial-targeted antioxidants may restrain production of ROS-mediated deleterious redox signalling pathways. If our hypothesis proves correct, therapeutic strategies directly targeting mitochondrial superoxide scavenging should be actively pursued as they may alleviate maternal vascular dysfunction and dramatically improve maternal and fetal health worldwide.

Butin reduces oxidative stress-induced mitochondrial dysfunction via scavenging of reactive oxygen species

2010 ◽  
Vol 48 (3) ◽  
pp. 922-927 ◽  
Author(s):  
Rui Zhang ◽  
Kyoung Ah Kang ◽  
Mei Jing Piao ◽  
Weon Young Chang ◽  
Young Hee Maeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Mitochondrial Dysfunction ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Survival Signaling by C-RAF: Mitochondrial Reactive Oxygen Species and Ca2+ Are Critical Targets

2008 ◽  
Vol 28 (7) ◽  
pp. 2304-2313 ◽  
Author(s):  
Andrey V. Kuznetsov ◽  
Julija Smigelskaite ◽  
Christine Doblander ◽  
Manickam Janakiraman ◽  
Martin Hermann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Ros ◽  
Survival Signaling ◽  
First Time

ABSTRACT Survival signaling by RAF occurs through largely unknown mechanisms. Here we provide evidence for the first time that RAF controls cell survival by maintaining permissive levels of mitochondrial reactive oxygen species (ROS) and Ca2+. Interleukin-3 (IL-3) withdrawal from 32D cells resulted in ROS production, which was suppressed by activated C-RAF. Oncogenic C-RAF decreased the percentage of apoptotic cells following treatment with staurosporine or the oxidative stress-inducing agent tert-butyl hydroperoxide. However, it was also the case that in parental 32D cells growing in the presence of IL-3, inhibition of RAF signaling resulted in elevated mitochondrial ROS and Ca2+ levels. Cell death is preceded by a ROS-dependent increase in mitochondrial Ca2+, which was absent from cells expressing transforming C-RAF. Prevention of mitochondrial Ca2+ overload after IL-3 deprivation increased cell viability. MEK was essential for the mitochondrial effects of RAF. In summary, our data show that survival control by C-RAF involves controlling ROS production, which otherwise perturbs mitochondrial Ca2+ homeostasis.

scholarly journals Dual and Opposite Roles of Reactive Oxygen Species (ROS) in Chagas Disease: Beneficial on the Pathogen and Harmful on the Host

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Edio Maldonado ◽  
Diego A. Rojas ◽  
Sebastian Morales ◽  
Vicente Miralles ◽  
Aldo Solari
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Oxidative Damage ◽  
Chagas Disease ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Parasite Growth ◽  
Oxygen Species ◽  
Chronic Stage ◽  
Mitochondrial Ros

Chagas disease is a neglected tropical disease, which affects an estimate of 6-7 million people worldwide. Chagas disease is caused by Trypanosoma cruzi, which is a eukaryotic flagellate unicellular organism. At the primary infection sites, these parasites are phagocytized by macrophages, which produce reactive oxygen species (ROS) in response to the infection with T. cruzi. The ROS produce damage to the host tissues; however, macrophage-produced ROS is also used as a signal for T. cruzi proliferation. At the later stages of infection, mitochondrial ROS is produced by the infected cardiomyocytes that contribute to the oxidative damage, which persists at the chronic stage of the disease. The oxidative damage leads to a functional impairment of the heart. In this review article, we will discuss the mechanisms by which T. cruzi is able to deal with the oxidative stress and how this helps the parasite growth at the acute phase of infection and how the oxidative stress affects the cardiomyopathy at the chronic stage of the Chagas disease. We will describe the mechanisms used by the parasite to deal with ROS and reactive nitrogen species (RNS) through the trypanothione and the mechanisms used to repair the damaged DNA. Also, a description of the events produced by ROS at the acute and chronic stages of the disease is presented. Lastly, we discuss the benefits of ROS for T. cruzi growth and proliferation and the possible mechanisms involved in this phenomenon. Hypothesis is put forward to explain the molecular mechanisms by which ROS triggers parasite growth and proliferation and how ROS is able to produce a long persisting damage on cardiomyocytes even in the absence of the parasite.

scholarly journals IP3Receptors, Mitochondria, and Ca2+Signaling: Implications for Aging

2011 ◽  
Vol 2011 ◽  
pp. 1-20 ◽  
Author(s):  
Jean-Paul Decuypere ◽  
Giovanni Monaco ◽  
Ludwig Missiaen ◽  
Humbert De Smedt ◽  
Jan B. Parys ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Aging Process ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Intracellular Ca ◽  
Uptake Mechanisms

The tight interplay between endoplasmic-reticulum-(ER-) and mitochondria-mediated Ca2+signaling is a key determinant of cellular health and cellular fate through the control of apoptosis and autophagy. Proteins that prevent or promote apoptosis and autophagy can affect intracellular Ca2+dynamics and homeostasis through binding and modulation of the intracellular Ca2+-release and Ca2+-uptake mechanisms. During aging, oxidative stress becomes an additional factor that affects ER and mitochondrial function and thus their role in Ca2+signaling. Importantly, mitochondrial dysfunction and sustained mitochondrial damage are likely to underlie part of the aging process. In this paper, we will discuss the different mechanisms that control intracellular Ca2+signaling with respect to apoptosis and autophagy and review how these processes are affected during aging through accumulation of reactive oxygen species.

scholarly journals Significance of Mitochondrial Reactive Oxygen Species in the Generation of Oxidative Stress in Spermatozoa

2008 ◽  
Vol 93 (8) ◽  
pp. 3199-3207 ◽  
Author(s):  
Adam J. Koppers ◽  
Geoffry N. De Iuliis ◽  
Jane M. Finnie ◽  
Eileen A. McLaughlin ◽  
R. John Aitken
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Complex I ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Human Spermatozoa ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Sperm Movement

Abstract Context: Male infertility has been linked with the excessive generation of reactive oxygen species (ROS) by defective spermatozoa. However, the subcellular origins of this activity are unclear. Objective: The objective of this study was to determine the importance of sperm mitochondria in creating the oxidative stress associated with defective sperm function. Method: Intracellular measurement of mitochondrial ROS generation and lipid peroxidation was performed using the fluorescent probes MitoSOX red and BODIPY C11 in conjunction with flow cytometry. Effects on sperm movement were measured by computer-assisted sperm analysis. Results: Disruption of mitochondrial electron transport flow in human spermatozoa resulted in generation of ROS from complex I (rotenone sensitive) or III (myxothiazol, antimycin A sensitive) via mechanisms that were independent of mitochondrial membrane potential. Activation of ROS generation at complex III led to the rapid release of hydrogen peroxide into the extracellular space, but no detectable peroxidative damage. Conversely, the induction of ROS on the matrix side of the inner mitochondrial membrane at complex I resulted in peroxidative damage to the midpiece and a loss of sperm movement that could be prevented by the concomitant presence of α-tocopherol. Defective human spermatozoa spontaneously generated mitochondrial ROS in a manner that was negatively correlated with motility. Simultaneous measurement of general cellular ROS generation with dihydroethidium indicated that 68% of the variability in such measurements could be explained by differences in mitochondrial ROS production. Conclusion: We conclude that the sperm mitochondria make a significant contribution to the oxidative stress experienced by defective human spermatozoa.

scholarly journals Propagation of Mitochondria-Derived Reactive Oxygen Species within the Dipodascus magnusii Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 120
Author(s):  
Anton G. Rogov ◽  
Tatiana N. Goleva ◽  
Khoren K. Epremyan ◽  
Igor I. Kireev ◽  
Renata A. Zvyagilskaya
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiac Myocytes ◽  
Mitochondrial Dynamics ◽  
Low Cost ◽  
Reactive Oxygen ◽  
Yeast Cells ◽  
Oxygen Species ◽  
Large Size ◽  
Mitochondrial Ros

Mitochondria are considered to be the main source of reactive oxygen species (ROS) in the cell. It was shown that in cardiac myocytes exposed to excessive oxidative stress, ROS-induced ROS release is triggered. However, cardiac myocytes have a network of densely packed organelles that do not move, which is not typical for the majority of eukaryotic cells. The purpose of this study was to trace the spatiotemporal development (propagation) of prooxidant-induced oxidative stress and its interplay with mitochondrial dynamics. We used Dipodascus magnusii yeast cells as a model, as they have advantages over other models, including a uniquely large size, mitochondria that are easy to visualize and freely moving, an ability to vigorously grow on well-defined low-cost substrates, and high responsibility. It was shown that prooxidant-induced oxidative stress was initiated in mitochondria, far preceding the appearance of generalized oxidative stress in the whole cell. For yeasts, these findings were obtained for the first time. Preincubation of yeast cells with SkQ1, a mitochondria-addressed antioxidant, substantially diminished production of mitochondrial ROS, while only slightly alleviating the generalized oxidative stress. This was expected, but had not yet been shown. Importantly, mitochondrial fragmentation was found to be primarily induced by mitochondrial ROS preceding the generalized oxidative stress development.

Are reactive oxygen species important mediators of vascular dysfunction?

2019 ◽  
Vol 15 ◽  
Author(s):  
Gabriel T. do Vale ◽  
Carlos R. Tirapelli
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiovascular Diseases ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Oxygen Metabolism ◽  
Ros Generation ◽  
Oxygen Species ◽  
Promising Alternative

Reactive oxygen species (ROS) are reactive derivatives of oxygen metabolism. The ROS generation can be mediated by distinctive enzymatic systems including NADPH oxidases. The components of this enzyme are expressed in endothelial and vascular smooth muscle cells, adventitial fibroblasts, and infiltrating monocytes/macrophages. Oxidative stress is a molecular dysregulation in ROS generation/elimination, which plays a key role in the development of vascular dysfunction in distinctive conditions including hypertension. It is characterized by vascular inflammation, a loss of NO bioavailability and endothelial dysfunction. Considering that oxidative stress is a key mediator of vascular dysfunction, antioxidant therapy with classic antioxidants seemed to be a promising alternative for the treatment of vascular diseases. In this sense, some commonly used drugs for the treatment of cardiovascular diseases such as angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor AT1 antagonists showed antioxidant effects that might have contributed, at least in part, to the beneficial effects of these drugs on the treatment of cardiovascular diseases. The effectiveness of these drugs shows that ROS are in fact important mediators of vascular dysfunction and that angiotensin II plays a critical role in such response.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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