scholarly journals Quantitative proteomic analysis reveals novel mitochondrial targets of estrogen deficiency in the aged female rat heart

2012 ◽  
Vol 44 (20) ◽  
pp. 957-969 ◽  
Author(s):  
T. S. Lancaster ◽  
S. J. Jefferson ◽  
J. Craig Hunter ◽  
Veronica Lopez ◽  
J. E. Van Eyk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adenine Nucleotide ◽  
Monoamine Oxidase A ◽  
Coronary Artery Ligation ◽  
Female Rat ◽  
Female Population ◽  
Ovx Rats ◽  
Age Related ◽  
Age Dependent ◽  
Mao A

The incidence of myocardial infarction rises sharply at menopause, implicating a potential role for estrogen (E2) loss in age-related increases in ischemic injury. We aimed to identify quantitative changes to the cardiac mitochondrial proteome of aging females, based on the hypothesis that E2 deficiency exacerbates age-dependent disruptions in mitochondrial proteins. Mitochondria isolated from left ventricles of adult (6 mo) and aged (24 mo) F344 ovary-intact or ovariectomized (OVX) rats were labeled with 8plex isobaric tags for relative and absolute quantification (iTRAQ; n = 5–6/group). Groups studied were adult, adult OVX, aged, and aged OVX. In vivo coronary artery ligation and in vitro mitochondrial respiration studies were also performed in a subset of rats. We identified 965 proteins across groups and significant directional changes in 67 proteins of aged and/or aged OVX; 32 proteins were unique to aged OVX. Notably, only six proteins were similarly altered in adult OVX (voltage-dependent ion channel 1, adenine nucleotide translocator 1, cytochrome c oxidase subunits VIIc and VIc, catalase, and myosin binding protein C). Proteins affected by aging were primarily related to cellular metabolism, oxidative stress, and cell death. The largest change occurred in monoamine oxidase-A (MAO-A), a source of oxidative stress. While acute MAO-A inhibition induced mild uncoupling in aged mitochondria, reductions in infarct size were not observed. Age-dependent alterations in mitochondrial signaling indicate a highly selective myocardial response to E2 deficiency. The combined proteomic and functional approaches described here offer possibility of new protein targets for experimentation and therapeutic intervention in the aged female population.

scholarly journals Oleuropein Aglycone Protects against MAO-A-Induced Autophagy Impairment and Cardiomyocyte Death through Activation of TFEB

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Caterina Miceli ◽  
Yohan Santin ◽  
Nicola Manzella ◽  
Raffaele Coppini ◽  
Andrea Berti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
Monoamine Oxidase A ◽  
Autophagic Flux ◽  
Cytotoxic Effects ◽  
Beneficial Effects ◽  
Age Related ◽  
Autophagy Induction ◽  
Mao A ◽  
Potential Use

Age-associated diseases such as neurodegenerative and cardiovascular disorders are characterized by increased oxidative stress associated with autophagy dysfunction. Oleuropein aglycone (OA), the main polyphenol found in olive oil, was recently characterized as an autophagy inducer and a promising agent against neurodegeneration. It is presently unknown whether OA can have beneficial effects in a model of cardiac stress characterized by autophagy dysfunction. Here, we explored the effects of OA in cardiomyocytes with overexpression of monoamine oxidase-A (MAO-A). This enzyme, by degrading catecholamine and serotonin, produces hydrogen peroxide (H2O2), which causes oxidative stress, autophagic flux blockade, and cell necrosis. We observed that OA treatment counteracted the cytotoxic effects of MAO-A through autophagy activation, as displayed by the increase of autophagic vacuoles and autophagy-specific markers (Beclin1 and LC3-II). Moreover, the decrease in autophagosomes and the increase in autolysosomes, indicative of autophagosome-lysosome fusion, suggested a restoration of the defective autophagic flux. Most interestingly, we found that the ability of OA to confer cardioprotection through autophagy induction involved nuclear translocation and activation of the transcriptional factor EB (TFEB). Our data provide strong evidence of the beneficial effects of OA, suggesting its potential use as a nutraceutical agent against age-related pathologies involving autophagy dysfunction, including cardiovascular diseases.

Age-dependent increase in hydrogen peroxide production by cardiac monoamine oxidase A in rats

2003 ◽  
Vol 284 (4) ◽  
pp. H1460-H1467 ◽  
Author(s):  
Agnès Maurel ◽  
Carole Hernandez ◽  
Oksana Kunduzova ◽  
Guy Bompart ◽  
Claudie Cambon ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Western Blot ◽  
Enzyme Assay ◽  
Monoamine Oxidase A ◽  
Pcr Analysis ◽  
Mao B ◽  
Age Related ◽  
Age Dependent ◽  
Mao A ◽  
Old Rats

Oxidative stress is one of the factors involved in age-related impairment of cardiac function. In the present study, we investigated the role of the catecholamine-degrading enzyme monoamine oxidase (MAO) in H2O2production in the hearts of young, adult, and old rats. MAO-dependent H2O2production, measured by a chemiluminescence-based assay, increased with age, reaching the maximum in 24-mo-old rats (7.5-fold increase vs. 1-mo-old rats). The following observations indicate that the age-dependent increase in H2O2generation was fully related to the MAO-A isoform: 1) at all the ages tested, chemiluminescence production was inhibited by the MAO-A inhibitor clorgyline but not by the MAO-B inhibitor RO-19 6327; 2) enzyme assay, Western blot, and semiquantitative RT-PCR analysis showed an age-dependent increase in cardiac MAO-A activity, immunodetection, and mRNA expression, respectively; and 3) the MAO-B isoform was undetectable by enzyme assay and Western blot analysis. These results suggest that MAO-A could be a major source of H2O2in the aging heart.

Brain monoamine oxidase A in hyperammonemia is regulated by NMDA receptors

2009 ◽  
Vol 4 (3) ◽  
pp. 321-326
Author(s):  
Elena Kosenko ◽  
Yury Kaminsky
Keyword(s):  
Oxidative Stress ◽  
Nmda Receptor ◽  
Monoamine Oxidase ◽  
Nmda Receptors ◽  
Monoamine Oxidase A ◽  
Mk 801 ◽  
Mao A ◽  
Vitro Effect

AbstractMitochondrial enzyme monoamine oxidase A (MAO-A) generates hydrogen peroxide (H2O2) and is up-regulated by Ca2+ and presumably by ammonia. We hypothesized that MAO-A may be under the control of NMDA receptors in hyperammonemia. In this work, the in vivo effects of single dosing with ammonia and NMDA receptor antagonist MK-801 and the in vitro effect of Ca2+ on MAO-A activity in isolated rat brain mitochondria were studied employing enzymatic procedure. Intraperitoneal injection of rats with ammonia led to an increase in MAO-A activity in mitochondria indicating excessive H2O2 generation. Calcium added to isolated mitochondria stimulated MAO-A activity by as much as 84%. MK-801 prevented the in vivo effect of ammonia, implying that MAO-A activation in hyperammonemia is mediated by NMDA receptors. These data support the conclusion that brain mitochondrial MAO-A is regulated by the function of NMDA receptors. The enzyme can contribute to the oxidative stress associated with hyperammonemic conditions such as encephalopathy and Alzheimer’s disease. The attenuation of the oxidative stress highlights MAO-A inactivation and NMDA receptor antagonists as sources of novel avenues in the treatment of mental disorders.

Antidepressant Effects of Vaccinium bracteatum via Protection Against Hydrogen Peroxide-Induced Oxidative Stress and Apoptosis

2018 ◽  
Vol 46 (07) ◽  
pp. 1499-1518 ◽  
Author(s):  
Dool-Ri Oh ◽  
Yujin Kim ◽  
Eun-Jin Choi ◽  
Ara Jo ◽  
Jawon Shin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Neuronal Damage ◽  
In Vitro Models ◽  
Monoamine Oxidase A ◽  
Protective Effects ◽  
Mao A ◽  
Anti Oxidant

The present study evaluates the anti-oxidative stress activity of Vaccinium bracteatum Thunb. fruit extract (VBFW) to identify the mechanisms responsible for its antidepressant-like effects. To evaluate the antidepressant and anti-oxidant effects of VBFW, malondialdehyde (MDA), serotonin transporter (SERT), and monoamine oxidase A (MAO-A) levels were measured in a mouse model of chronic restraint stress (CRS). The underlying mechanisms preventing oxidative stress and neuronal apoptosis were investigated using in vitro models of hydrogen peroxide (H2O[Formula: see text]-induced neuronal damage. The results showed that VBFW treatment (200[Formula: see text]mg/kg) significantly reduced MDA, SERT, and MAO-A levels in the prefrontal cortex of CRS mice. Furthermore, VBFW (30[Formula: see text][Formula: see text]g/mL) exhibited protective effects against H2O2-induced cell death via inhibition of the H2O2-induced increase in Bax and decrease in Bcl-2 levels within the mitochondria of SH-SY5Y cells. Furthermore, VBFW (10 and 30[Formula: see text][Formula: see text]g/mL) exerted protective effects against H2O2-induced cell death through inhibition of key mitochondria-associated apoptotic proteins such as cytochrome c, caspase-3 and PARP. Additionally, VBFW (10 and 30[Formula: see text][Formula: see text]g/mL) could improve the activity of anti-oxidant enzymes (such as SOD and catalase) in H2O2-treated SH-SY5Y cells. These results suggest that the antidepressant and anti-oxidant effects of VBFW might be mediated by the regulation of SERT and MAO-A, and possibly associated with regulation of oxidative stress-induced apoptosis.

scholarly journals Depletion of the Third Complement Component Ameliorates Age-Dependent Oxidative Stress and Positively Modulates Autophagic Activity in Aged Retinas in a Mouse Model

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Dorota Rogińska ◽  
Miłosz P. Kawa ◽  
Ewa Pius-Sadowska ◽  
Renata Lejkowska ◽  
Karolina Łuczkowska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Global Gene Expression ◽  
Complement Component ◽  
Oxidative Stress Marker ◽  
Age Related ◽  
Age Dependent ◽  
Autophagic Activity

The aim of the study was to investigate the influence of complement component C3 global depletion on the biological structure and function of the aged retina. In vivo morphology (OCT), electrophysiological function (ERG), and the expression of selected oxidative stress-, apoptosis-, and autophagy-related proteins were assessed in retinas of 12-month-old C3-deficient and WT mice. Moreover, global gene expression in retinas was analyzed by RNA arrays. We found that the absence of active C3 was associated with (1) alleviation of the age-dependent decrease in retinal thickness and gradual deterioration of retinal bioelectrical function, (2) significantly higher levels of antioxidant enzymes (catalase and glutathione reductase) and the antiapoptotic survivin and Mcl-1/Bak dimer, (3) lower expression of the cellular oxidative stress marker—4HNE—and decreased activity of proapoptotic caspase-3, (4) ameliorated retinal autophagic activity with localization of ubiquitinated protein conjugates commonly along the retinal pigment epithelium (RPE) layer, and (5) significantly increased expression of several gene sets associated with maintenance of the physiological functions of the neural retina. Our findings shed light on mechanisms of age-related retinal alterations by identifying C3 as a potential therapeutic target for retinal aging.

scholarly journals Plasma Protein Oxidation and Its Correlation with Antioxidant Potential During Human Aging

2010 ◽  
Vol 29 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Kanti Bhooshan Pandey ◽  
Mohd Murtaza Mehdi ◽  
Pawan Kumar Maurya ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Plasma Protein ◽  
Protein Oxidation ◽  
Cellular Systems ◽  
Antioxidant Potential ◽  
Protein Carbonyls ◽  
Oxidized Proteins ◽  
Oxidative Damages ◽  
Age Related ◽  
Age Dependent

Previous studies have indicated that the main molecular characteristic of aging is the progressive accumulation of oxidative damages in cellular macromolecules. Proteins are one of the main molecular targets of age-related oxidative stress, which have been observed during aging process in cellular systems. Reactive oxygen species (ROS) can lead to oxidation of amino acid side chains, formation of protein-protein cross-linkages, and oxidation of the peptide backbones. In the present study, we report the age-dependent oxidative alterations in biomarkers of plasma protein oxidation: protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and plasma total thiol groups (T-SH) in the Indian population and also correlate these parameters with total plasma antioxidant potential. We show an age dependent decrease in T-SH levels and increase in PCO and AOPPs level. The alterations in the levels of these parameters correlated significantly with the total antioxidant capacity of the plasma. The levels of oxidized proteins in plasma provide an excellent biomarker of oxidative stress due to the relative long half-life of such oxidized proteins.

scholarly journals Selective Cardiomyocyte Oxidative Stress Leads to Bystander Senescence of Cardiac Stromal Cells

2021 ◽  
Vol 22 (5) ◽  
pp. 2245
Author(s):  
Hélène Martini ◽  
Lise Lefevre ◽  
Sylvain Sayir ◽  
Romain Itier ◽  
Damien Maggiorani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Cardiac Dysfunction ◽  
Accelerated Aging ◽  
Monoamine Oxidase A ◽  
Premature Senescence ◽  
Age Related ◽  
Stress Dependent ◽  
Stress Induced Premature Senescence ◽  
The Impact

Accumulation of senescent cells in tissues during normal or accelerated aging has been shown to be detrimental and to favor the outcomes of age-related diseases such as heart failure (HF). We have previously shown that oxidative stress dependent on monoamine oxidase A (MAOA) activity in cardiomyocytes promotes mitochondrial damage, the formation of telomere-associated foci, senescence markers, and triggers systolic cardiac dysfunction in a model of transgenic mice overexpressing MAOA in cardiomyocytes (Tg MAOA). However, the impact of cardiomyocyte oxidative stress on the cardiac microenvironment in vivo is still unclear. Our results showed that systolic cardiac dysfunction in Tg MAOA mice was strongly correlated with oxidative stress induced premature senescence of cardiac stromal cells favoring the recruitment of CCR2+ monocytes and the installation of cardiac inflammation. Understanding the interplay between oxidative stress induced premature senescence and accelerated cardiac dysfunction will help to define new molecular pathways at the crossroad between cardiac dysfunction and accelerated aging, which could contribute to the increased susceptibility of the elderly to HF.

The role of p66Shc deletion in age-associated arterial dysfunction and disease states

2008 ◽  
Vol 105 (5) ◽  
pp. 1628-1631 ◽  
Author(s):  
Giovanni G. Camici ◽  
Francesco Cosentino ◽  
Felix C. Tanner ◽  
Thomas F. Lüscher
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Adaptor Protein ◽  
Oxygen Species ◽  
Potential Implication ◽  
Disease States ◽  
Age Related ◽  
Related Risk ◽  
Age Dependent

Accumulation of oxidative stress with age is hypothesized to be the primary causative mediator of age-associated diseases. Among different tissues, aging vessels are known to accumulate oxidative damage and undergo functional impairment. Oxidative stress affects the availability and/or balance of key regulators of vascular homeostasis and favors the development of cardiovascular disease. Reactive oxygen species are generated by different intracellular molecular pathways principally located in the cytoplasm and in the mitochondria. The mitochondrial enzyme p66Shc is an adaptor protein and plays an important role as a redox enzyme implicated in mitochondrial eactive oxygen species generation and translation of oxidative signals into apoptosis. Mice lacking p66Shc−/− gene display reduced production of intracellular oxidants and a 30% prolonged life span. For this reasons, a series of studies conceived to elucidate the function of p66Shc and its possible implication in age-associated cardiovascular diseases have been carried out. Indeed, p66Shc−/− mice have been shown to be protected from age-dependent endothelial dysfunction as well as age-related risk factors such as diabetes and hypercholesterolemia. This review focuses on delineating the role of the p66Shc adaptor protein and its potential implication in the pathophysiology of aging and age-related cardiovascular disease.

scholarly journals Oxidative damage to DNA and antioxidant status in aging and age-related diseases.

2007 ◽  
Vol 54 (1) ◽  
pp. 11-26 ◽  
Author(s):  
Ryszard Olinski ◽  
Agnieszka Siomek ◽  
Rafal Rozalski ◽  
Daniel Gackowski ◽  
Marek Foksinski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Single Cells ◽  
Cellular Level ◽  
Pathological Conditions ◽  
Age Related ◽  
Complex Process ◽  
Age Dependent ◽  
Oxidatively Modified ◽  
Oxidative Damage To Dna

Aging is a complex process involving morphologic and biochemical changes in single cells and in the whole organism. One of the most popular explanations of how aging occurs at the molecular level is the oxidative stress hypothesis. Oxidative stress leads in many cases to an age-dependent increase in the cellular level of oxidatively modified macromolecules including DNA, and it is this increase which has been linked to various pathological conditions, such as aging, carcinogenesis, neurodegenerative and cardiovascular diseases. It is, however, possible that a number of short-comings associated with gaps in our knowledge may be responsible for the failure to produce definite results when applied to understanding the role of DNA damage in aging and age-related diseases.

scholarly journals Prevalence rate of cornea diseases according materials of outpatient facilities in Baku city

2021 ◽  
Vol 14 (2) ◽  
pp. 23-26
Author(s):  
P. M. Maharramov
Keyword(s):  
Infectious Diseases ◽  
Prevalence Rate ◽  
Age Groups ◽  
Older Age ◽  
Male Population ◽  
Female Population ◽  
Age Related ◽  
Age Dependent ◽  
The City

Purpose: to assess the prevalence of corneal diseases using the data on the incidence of visits to outpatient facilities in the city of Baku. Material and methods. The data, presented by outpatient facilities for the year 2017, were statistically analyzed. Results. It was revealed that, for every 100 000 people, there were 266.1±3.4 cases of corneal diseases of which 97.9 ± 2.1 were infectious and 166.9 ± 2.7 were noninfectious diseases. Corneal neoplasms were detected in 1.3 ± 0.2 cases. The ratio of non-infectious and infectious diseases ofthe cornea was ca. 1.7. The lowest prevalence rate of both infectious and non-infectious diseases of the cornea was detected in children aged 0 to 9 years. In older age groups, the change of prevalence of corneal diseases was found to be chaotic. The trends of age-related prevalenceof infectious vs. non-infectious diseases of the cornea were basically similar; the highest rate was detected among patients aged 60–69. Conclusion.According to the appealability data, the prevalence rate of corneal diseases is rather high and age-dependent with a prevailing share of non-infectious corneal pathologies. In male population, this rate is notably lower than in female population.

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