Running Low But Long: Mutation in energy production machinery extends life in worms (Oxidative stress)

Accumulating evidence support the cardioprotective properties of the nuclear receptor peroxisome proliferator activated receptor β/δ (PPARβ/δ); however, the underlying mechanisms are not yet fully elucidated. The aim of the study was to further investigate the mechanisms underlying PPARβ/δ-mediated cardioprotection in the setting of myocardial ischemia/reperfusion (I/R). For this purpose, rats were treated with PPARβ/δ agonist GW0742 and/or antagonist GSK0660 in vivo and hearts were subjected to ex vivo global ischemia followed by reperfusion. PPARβ/δ activation improved left ventricular developed pressure recovery, reduced infarct size (IS) and incidence of reperfusion-induced ventricular arrhythmias while it also up-regulated superoxide dismutase 2, catalase and uncoupling protein 3 resulting in attenuation of oxidative stress as evidenced by the reduction in 4-hydroxy-2-nonenal protein adducts and protein carbonyl formation. PPARβ/δ activation also increased both mRNA expression and enzymatic activity of aldehyde dehydrogenase 2 (ALDH2); inhibition of ALDH2 abrogated the IS limiting effect of PPARβ/δ activation. Furthermore, upregulation of PGC-1α and isocitrate dehydrogenase 2 mRNA expression, increased citrate synthase activity as well as mitochondrial ATP content indicated improvement in mitochondrial content and energy production. These data provide new mechanistic insight into the cardioprotective properties of PPARβ/δ in I/R pointing to ALDH2 as a direct downstream target and suggesting that PPARβ/δ activation alleviates myocardial I/R injury through coordinated stimulation of the antioxidant defense of the heart and preservation of mitochondrial function.

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Abstract 276: Angiotensin AT1 Receptor Blockade Reverses Age-Related Changes in Myocardial Energy Metabolism and Increases Mitochondrial Biogenesis

Hypertension ◽

10.1161/hyp.60.suppl_1.a276 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Peter M Abadir ◽

Ashwin Akki ◽

Robert Carey ◽

Ashish Gupta ◽

Vadappuram Chacko ◽

...

Keyword(s):

Oxidative Stress ◽

Energy Metabolism ◽

Mitochondrial Biogenesis ◽

Energy Production ◽

Nuclear Gene ◽

At1 Receptor ◽

Resonance Spectroscopy ◽

Receptor Blockade ◽

Lv Mass ◽

Old Mice

Aging and mitochondrial function have been closely linked. We recently reported the identification of a mitochondrial angiotensin system. We hypothesized that angiotensin AT1 receptor blockade would increase energy production and mitochondrial biogenesis and reduce oxidative stress in aging hearts. We used Magnetic resonance spectroscopy to measure cardiac energy metabolism and function in young (20 wks old), aged (150 wks old) mice at baseline and after 4 weeks of losartan (50 mg/kg/day). For mitobiogenesis, qPCR was used to calculate CytB (mitochondrial gene)/GAPDH (nuclear gene) ratio and to measure mito-survival genes Sirt1, Sirt3, Nampt, and PGC-1α. Cardiomyocyte mitochondria from young, aged and treated mice were examined with electron microscopy. The expression of nitrotyrosine was quantified by immunohistochemistry. Older animals hearts (n=9) exhibited increase in LV mass (103±9 mg versus 120±8 mg, young (n=8) versus old (n=9), P<0.002). The mean cardiac PCr/ATP was reduced in older animals (1.5±0.2) than that of young mice (2.0±0.3, P<0.0004). Losartan abolished the LV mass increase in older animals (109±11 mg vs 101±7 mg, young versus old, P<0.1) and improved the impaired energy metabolism of the older hearts increasing the PCr/ATP ratios towards those observed in younger animals (1.94±0.01 vs 1.87±0.4, control versus old, P<0.7). Losartan increased EF in older animals (56±5% vs 63±5%, old versus old treated, P<0.01). Losartan increased mitobiogenesis in the hearts of treated young and old mice (3.8+2.5 folds, P<0.02 and 4.3+ 0.9 folds, P<0.0001). Mito-survival genes in the heart were not increased but PGC-1α was up-regulated by 2.8+1.6-fold, P<0.05 and 7+ 1.9-fold, P<0.001 in young and old treated mice. Electron micrograph analysis revealed that aging was associated with swollen cardiac mitochondria and disrupted cristae, which were reversed by Losartan. Losartan in older animals significantly reduced oxidative damage as evidenced by less Nitrotyrosine staining score in cardiomyocytes (2.5±0.5 vs. 1.3±0.4, old versus old treated, P<0.0009). Our results indicate that Losartan in aging increased mitobiogenesis, reduced oxidative stress, improved energy production and restored cardiac function to the healthy young adult level.

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Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress

PLoS Biology ◽

10.1371/journal.pbio.1002197 ◽

2015 ◽

Vol 13 (7) ◽

pp. e1002197 ◽

Cited By ~ 29

Author(s):

Manish Jaiswal ◽

Nele A. Haelterman ◽

Hector Sandoval ◽

Bo Xiong ◽

Taraka Donti ◽

...

Keyword(s):

Oxidative Stress ◽

Energy Production ◽

Photoreceptor Degeneration ◽

Mitochondrial Energy Production

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Broad scale proteomic analysis of heat-destabilised symbiosis in the hard coral Acropora millepora

Scientific Reports ◽

10.1038/s41598-021-98548-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

K. Petrou ◽

B. L. Nunn ◽

M. P. Padula ◽

D. J. Miller ◽

D. A. Nielsen

Keyword(s):

Oxidative Stress ◽

Elevated Temperature ◽

Energy Production ◽

Hard Coral ◽

Host Proteins ◽

Acropora Millepora ◽

Cytoskeletal Regulation ◽

Lipid Stores ◽

Broad Scale ◽

Incremental Increase

AbstractCoral reefs across the globe are threatened by warming oceans. The last few years have seen the worst mass coral bleaching events recorded, with more than one quarter of all reefs irreversibly impacted. Considering the widespread devastation, we need to increase our efforts to understanding the physiological and metabolic shifts underlying the breakdown of this important symbiotic ecosystem. Here, we investigated the proteome (PRIDE accession # PXD011668) of both host and symbionts of the reef-building coral Acropora millepora exposed to ambient (~ 28 °C) and elevated temperature (~ 32 °C for 2 days, following a five-day incremental increase) and explored associated biomolecular changes in the symbiont, with the aim of gaining new insights into the mechanisms underpinning the collapse of the coral symbiosis. We identified 1,230 unique proteins (774 host and 456 symbiont) in the control and thermally stressed corals, of which 107 significantly increased and 125 decreased in abundance under elevated temperature relative to the control. Proteins involved in oxidative stress and proteolysis constituted 29% of the host proteins that increased in abundance, with evidence of impairment to endoplasmic reticulum and cytoskeletal regulation proteins. In the symbiont, we detected a decrease in proteins responsible for photosynthesis and energy production (33% of proteins decreased in abundance), yet minimal signs of oxidative stress or proteolysis. Lipid stores increased > twofold despite reduction in photosynthesis, suggesting reduced translocation of carbon to the host. There were significant changes in proteins related to symbiotic state, including proteins linked to nitrogen metabolism in the host and the V-ATPase (-0.6 fold change) known to control symbiosome acidity. These results highlight key differences in host and symbiont proteomic adjustments under elevated temperature and identify two key proteins directly involved in bilateral nutrient exchange as potential indicators of symbiosis breakdown.

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Mitophagy and Oxidative Stress in Cancer and Aging: Focus on Sirtuins and Nanomaterials

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6387357 ◽

2019 ◽

Vol 2019 ◽

pp. 1-19 ◽

Cited By ~ 10

Author(s):

Enza Vernucci ◽

Carlo Tomino ◽

Francesca Molinari ◽

Dolores Limongi ◽

Michele Aventaggiato ◽

...

Keyword(s):

Oxidative Stress ◽

Energy Production ◽

Structural Adjustment ◽

Molecular Targets ◽

Production Loss ◽

Cellular Adaptation ◽

Invasive Strategy ◽

Age Related ◽

New Frontier ◽

And Oxidative Stress

Mitochondria are the cellular center of energy production and of several important metabolic processes. Mitochondrion health is maintained with a substantial intervention of mitophagy, a process of macroautophagy that degrades selectively dysfunctional and irreversibly damaged organelles. Because of its crucial duty, alteration in mitophagy can cause functional and structural adjustment in the mitochondria, changes in energy production, loss of cellular adaptation, and cell death. In this review, we discuss the dual role that mitophagy plays in cancer and age-related pathologies, as a consequence of oxidative stress, evidencing the triggering stimuli and mechanisms and suggesting the molecular targets for its therapeutic control. Finally, a section has been dedicated to the interplay between mitophagy and therapies using nanoparticles that are the new frontier for a direct and less invasive strategy.

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Correction: Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress

PLoS Biology ◽

10.1371/journal.pbio.1002622 ◽

2018 ◽

Vol 16 (3) ◽

pp. e1002622 ◽

Cited By ~ 1

Author(s):

Manish Jaiswal ◽

Nele A. Haelterman ◽

Hector Sandoval ◽

Bo Xiong ◽

Taraka Donti ◽

...

Keyword(s):

Oxidative Stress ◽

Energy Production ◽

Photoreceptor Degeneration ◽

Mitochondrial Energy Production

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Mitochondrial Dysfunctions and Altered Metals Homeostasis: New Weapons to Counteract HCV-Related Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/971024 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 18

Author(s):

Mario Arciello ◽

Manuele Gori ◽

Clara Balsano

Keyword(s):

Oxidative Stress ◽

Free Radicals ◽

Metabolic Pathways ◽

Energy Production ◽

Power Plants ◽

Focal Point ◽

Antioxidant Defenses ◽

Host Organism ◽

Mitochondrial Dysfunctions

The hepatitis C virus (HCV) infection produces several pathological effects in host organism through a wide number of molecular/metabolic pathways. Today it is worldwide accepted that oxidative stress actively participates in HCV pathology, even if the antioxidant therapies adopted until now were scarcely effective. HCV causes oxidative stress by a variety of processes, such as activation of prooxidant enzymes, weakening of antioxidant defenses, organelle damage, and metals unbalance. A focal point, in HCV-related oxidative stress onset, is the mitochondrial failure. These organelles, known to be the “power plants” of cells, have a central role in energy production, metabolism, and metals homeostasis, mainly copper and iron. Furthermore, mitochondria are direct viral targets, because many HCV proteins associate with them. They are the main intracellular free radicals producers and targets. Mitochondrial dysfunctions play a key role in the metal imbalance. This event, today overlooked, is involved in oxidative stress exacerbation and may play a role in HCV life cycle. In this review, we summarize the role of mitochondria and metals in HCV-related oxidative stress, highlighting the need to consider their deregulation in the HCV-related liver damage and in the antiviral management of patients.

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The role of glutamine synthetase in energy production and glutamine metabolism during oxidative stress

Antonie van Leeuwenhoek ◽

10.1007/s10482-017-0829-3 ◽

2017 ◽

Vol 110 (5) ◽

pp. 629-639 ◽

Cited By ~ 12

Author(s):

Nohaiah Aldarini ◽

Azhar A. Alhasawi ◽

Sean C. Thomas ◽

Vasu D. Appanna

Keyword(s):

Oxidative Stress ◽

Glutamine Synthetase ◽

Energy Production ◽

Glutamine Metabolism

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EFFECT OF N-ACETYLCARNOSINE CONTAINED EYE DROP ON CATECHOLAMINE-INDUCED MORPHOFUNCTIONAL DAMAGE IN RAT RETINA

Fiziolohichnyĭ zhurnal ◽

10.15407/fz66.04.064 ◽

2020 ◽

Vol 66 (4) ◽

pp. 64-71

Author(s):

V.V. Sanin ◽

◽

A.I. Yakovets ◽

K.V. Rozova ◽

Yu.P. Korkach ◽

...

Keyword(s):

Oxidative Stress ◽

Energy Production ◽

Wistar Rats ◽

Antioxidant Effect ◽

Compensatory Mechanism ◽

Oxygen Species ◽

Rat Retina ◽

Eye Tissues ◽

Markers Of Oxidative Stress ◽

Adrenaline Administration

The effects of N-acetylcarnosine (NAC)-contained eye drop ‘Clarastil’ on a model of adrenaline-induced high intraocular pressure (IOP) in Wistar rats were studied. The retina ultrastructure and markers of oxidative stress have been studied. NAC was found to have no significant effect on edema in the retinal ultrastructure, did not reduce endothelial thickening and histogemic barrier, and accordingly did not affect the value of IOP after prolonged adrenaline administration. However, the introduction of the eye drop prevented the swelling of the mitochondria, the formation of vacuolated crystals and probably stimulated energy production as a compensatory mechanism under conditions of hypercatecholemia. In addition, NAC significantly reduced adrenaline-induced overproduction of reactive oxygen species and lipid peroxidation products in eye tissues, indicating its antioxidant effect.

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