scholarly journals Clueless forms dynamic, insulin-responsive bliss particles sensitive to stress

2019 ◽  
Author(s):  
K. M. Sheard ◽  
S. A. Thibault-Sennett ◽  
A. Sen ◽  
F. Shewmaker ◽  
R. T. Cox
Keyword(s):  
Oxidative Stress ◽  
Metabolic Stress ◽  
Particle Formation ◽  
Optimal Conditions ◽  
Atp Production ◽  
Protein Levels ◽  
Cytoplasmic Bodies ◽  
Mitochondrial Functions ◽  
Large Particles ◽  
Necessary And Sufficient

AbstractMitochondria perform a myriad of biochemical functions in the cell that integrate ATP production and metabolism. While mitochondria contain their own genome, mtDNA, it only encodes thirteen proteins required for oxidative phosphorylation, thus well over one thousand proteins required for all mitochondrial functions are encoded in the nucleus. One such protein is Drosophila Clueless (Clu), whose vertebrate homolog is Clustered mitochondria homolog (Cluh). Clu/Cluh is a ribonucleoprotein that regulates mRNAs destined for import into mitochondria and is an essential protein that regulates cellular metabolism. Clu forms large particles in the cytoplasm, although how these particles relate to nutrition and metabolic stress is unknown. Using live-imaging, we show Clu particles are highly dynamic. Clu particles appear to be unique as they do not colocalize with many known cytoplasmic bodies. In addition, Clu particle formation is highly dependent on diet as ovaries from starved females no longer contain Clu particles although Clu protein levels remain the same and insulin is necessary and sufficient for Clu particle formation. Oxidative stress also disperses particle. Since Clu particles are only present under optimal conditions we are naming them bliss particles. These observations identify Clu particles as unique, stress-sensitive cytoplasmic ribonucleoprotein particles whose absence corresponds with altered mitochondrial function and localization.

scholarly journals Honeybush Extracts (Cyclopia spp.) Rescue Mitochondrial Functions and Bioenergetics against Oxidative Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Anastasia Agapouda ◽  
Veronika Butterweck ◽  
Matthias Hamburger ◽  
Dalene de Beer ◽  
Elizabeth Joubert ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Hot Water ◽  
Human Neuroblastoma ◽  
Atp Production ◽  
Physiological Conditions ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Scientific Attention

Mitochondrial dysfunction plays a major role not only in the pathogenesis of many oxidative stress or age-related diseases such as neurodegenerative as well as mental disorders but also in normal aging. There is evidence that oxidative stress and mitochondrial dysfunction are the most upstream and common events in the pathomechanisms of neurodegeneration. Cyclopia species are endemic South African plants and some have a long tradition of use as herbal tea, known as honeybush tea. Extracts of the tea are gaining more scientific attention due to their phenolic composition. In the present study, we tested not only the in vitro mitochondria-enhancing properties of honeybush extracts under physiological conditions but also their ameliorative properties under oxidative stress situations. Hot water and ethanolic extracts of C. subternata, C. genistoides, and C. longifolia were investigated. Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts, at a concentration range of 0.1-1 ng/ml, had a beneficial effect on bioenergetics as it increased ATP production, respiration, and mitochondrial membrane potential (MMP) after 24 hours under physiological conditions. The aqueous extracts of C. subternata and C. genistoides, in particular, showed a protective effect by rescuing the bioenergetic and mitochondrial deficits under oxidative stress conditions (400 μM H2O2 for 3 hours). These findings indicate that honeybush extracts could constitute candidates for the prevention of oxidative stress with an impact on aging processes and age-related neurodegenerative disorders potentially leading to the development of a condition-specific nutraceutical.

scholarly journals Acidic ambiance induced post-oxidative stress affects AMPK- PGC1α-SIRT1 axis in the skeletal muscles of zebrafish Danio rerio Hamilton, 1822

2021 ◽  
Vol 64 (2) ◽  
pp. 191-198
Author(s):  
Sabarna Chowdhury ◽  
Subhendu K. Chatterjee ◽  
Samir Bhattacharya ◽  
Sudipta Maitra ◽  
Surjya K. Saikia
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Mitochondrial Gene ◽  
Adaptive Strategy ◽  
Atp Production ◽  
Mitochondrial Functions ◽  
Metabolic Sensor ◽  
Metabolic Disruption ◽  
Complex I Activity

The present study was aimed to understand whether acidic pH induces oxidative stress in zebrafish affecting metabolic sensor protein and thereby, the mitochondrial functions in the skeletal muscle of zebrafish. The experiments performed in aquaria involved the study of the changes of HIF1α, AMPK, PGC1α and SIRT1 levels together with the levels of mitochondrial Tfam and Nrf1. The results obtained from investigation of superoxide dismutase (SOD), catalase and glutathione revealed that the fish undergoes oxidative stress within a short duration of exposure to acidic ambiance. Further analysis with MDA and HIF1α helped to understand the effects of post oxidative stress on skeletal muscle of the fish at pH 5.0 (± 0.5). Of the three tissues studied (gill, brain and skeletal muscle) the effect was maximum in skeletal muscle as depicted by MDA level at 2 hours beyond which it declines augmenting death or mortality (15%) to the fish. Consequently, HIF1α was increased as an adaptive strategy against metabolic disruption during the first 2 hours period. However, on exposure to pH 5.0 (± 0.5) for 2 hours, there were decrease of the metabolic sensors viz. AMPK and SIRT1 followed by mitochondrial gene transcriptional co-activator PGC1α. The expression of mitochon-drial transcription factors Tfam and Nrf1 were also reduced confirming perturbation in mitochondrial function affecting low ATP production compared to control. This was also supported by the decrease of COXII as well as mitochondrial complex I activity. All these results confirm that the metabolic machinery of zebrafish is affected when pH was lowered to 5.0 (± 0.5).

scholarly journals Cucurbitacin I Protects H9c2 Cardiomyoblasts against H2O2-Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Dong Kwon Yang ◽  
Shang-Jin Kim
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Cardiac Cells ◽  
Ros Production ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Protein Levels ◽  
Mitochondrial Functions ◽  
H9c2 Cardiomyoblasts ◽  
Antioxidant Effects

Cucurbitacin I, a triterpenoid natural compound, exhibits various pharmacological properties, including anticancer, anti-inflammatory, and hepatoprotective properties. However, antioxidant effects of cucurbitacin I in cardiac cells are currently unknown. In the present study, we assessed the preventive effects of cucurbitacin I against the oxidative stress in H9c2 cardiomyoblasts. To evaluate antioxidant effects of cucurbitacin I in H9c2 cardiomyoblasts, H2O2-treated H9c2 cells were pretreated with various concentrations of the cucurbitacin I. Cell viability, reactive oxygen species (ROS) production, and apoptosis were determined to elucidate the protective effects of cucurbitacin I against H2O2-induced oxidative stress in H9c2 cells. In addition, we assessed the mitochondrial functions and protein expression levels of mitogen-activated protein kinases (MAPKs). Cucurbitacin I prevented the cells against cell death and ROS production and elevated the antioxidant protein levels upon oxidative stress. Furthermore, cucurbitacin I preserved the mitochondrial functions and inhibited the apoptotic responses in H2O2-treated cells. Cucurbitacin I also suppressed the activation of MAPK proteins (extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38). Collectively, cucurbitacin I potentially protects the H9c2 cardiomyoblasts against oxidative stress and further suggests that it can be utilized as a therapeutic agent for the prevention of oxidative stress in cardiac injury.

Upregulation of mitochondrial E3 ubiquitin ligase 1 in rat heart contributes to ischemia/reperfusion injury

2020 ◽  
Vol 98 (5) ◽  
pp. 259-266 ◽  
Author(s):  
Shi-Jing Wang ◽  
Heng Chen ◽  
Li-Jing Tang ◽  
Hua Tu ◽  
Bin Liu ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitochondrial Protein ◽  
E3 Ubiquitin Ligase ◽  
Sprague Dawley ◽  
Mitochondrial Dysfunctions ◽  
Atp Production ◽  
Protein Levels ◽  
Mitochondrial Functions

Mitochondrial dysfunctions are responsible for myocardial injury upon ischemia/reperfusion (I/R), and mitochondrial E3 ubiquitin ligase 1 (Mul1) plays an important role in maintaining mitochondrial functions. This study aims to explore the function of Mul1 in myocardial I/R injury and the underlying mechanisms. The Sprague–Dawley rat hearts were subjected to 1 h of ischemia plus 3 h of reperfusion, which showed the I/R injury (increase in infarct size and creatine kinase release) and the elevated total and mitochondrial protein levels of Mul1 and p53 accompanied by the enhanced interactions between Mul1 and p53 as well as p53 and small a ubiquitin-like modifier (SUMO1). Consistently, hypoxia/reoxygenation (H/R) treated cardiac (H9c2) cells displayed cellular injury (apoptosis and necrosis), upregulation of total and mitochondrial protein levels of Mul1 and p53, and enhanced interactions between p53 and SUMO1 concomitant with mitochondrial dysfunctions (an increase in mitochondrial membrane potential and reactive oxygen species production with a decrease in ATP production); these phenomena were attenuated by knockdown of Mul1 expression. Based on these observations, we conclude that a novel role of Mul1 has been identified in the myocardial mitochondria, where Mul1 stabilizes and activates p53 through its function of SUMOylation following I/R, leading to p53-mediated mitochondrial dysfunction and cell death.

scholarly journals CFTR improves myocardial ischemic/reperfusion injury through activating FUNDC1-mediated mitophagy and regulating ATP and mitochondrial functions

2020 ◽  
Author(s):  
Yaping Zhang ◽  
Nan Ding ◽  
Hanlu Yi ◽  
Yudong Zhao ◽  
Daole Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Protein Levels ◽  
Ischemic Reperfusion ◽  
Atp Concentration ◽  
Mitochondrial Functions ◽  
Tnf Α ◽  
Apoptosis Related Protein ◽  
Related Proteins

Abstract Background To investigate the potential role of CFTR in myocardial ischemic/reperfusion (I/R) injury and its relationship with mitophagy. Methods Wild type (WT) and age matched CFTR−/− male mice were used to establish the myocardial I/R model. CFTR activator forskolin (FSK) was used to activate CFTR in mice. Hypoxia/reoxygenation (H/R) treatment was used for in vitro model in WT or CFTR−/− cardiomyocytes. The autophagy inhibitor 3-MA and activator rapamycin was used for inhibition or activation of autophagy, respectively. The mitochondrial membrane potential (MMP) and ATP concentration were detected. Immunofluorescence was performed for measurement of mitochondria. Oxidative factors reactive oxygen species (ROS), superoxide dismutase (SOD), malondiadehycle (MDA) and glutathione peroxidase (GSH-PX) were detected. The expression of CFTR, MMP-9, TNF-α, IL-8, LC3 II/I, beclin1, caspase-3, caspase-8, caspase-9, bax, bcl-2, p-62 and FUNDC1 was determined using western blotting or PCR. Results Knockdown of CFTR significantly increased the infraction volume and decreased the expression of autophagy related proteins beclin1 and LC3II/I in mice. In H/R cardiomyocytes, deficiency of CFTR by induced dysfunction of mitochondrial, decrease of ATP concentration and enhanced oxidative stress, as well as inhibited mitophagy and increased cell apoptosis related protein levels. When treated with 3-MA, the effects of overexpression of CFTR was remarkably reversed, while treatment of rapamycin significantly reversed the effects of inhibiting CFTR on both mitophagy, oxidative stress and cell apoptosis related proteins. The inhibition of FUNDC1 also reversed the above effects of overexpressing CFTR. Conclusion Inhibition of CFTR could promote myocardial I/R injury by suppressing FUNDC1-mediated mitophagy and activating of oxidative stress.

scholarly journals Cinnamon Oil Inhibits Penicillium expansum Growth by Disturbing the Carbohydrate Metabolic Process

2021 ◽  
Vol 7 (2) ◽  
pp. 123
Author(s):  
Tongfei Lai ◽  
Yangying Sun ◽  
Yaoyao Liu ◽  
Ran Li ◽  
Yuanzhi Chen ◽  
...  
Keyword(s):  
Pentose Phosphate ◽  
Metabolic Process ◽  
Penicillium Expansum ◽  
Economic Losses ◽  
Pome Fruit ◽  
Cinnamon Oil ◽  
Atp Production ◽  
Protein Levels ◽  
Regulatory Enzymes ◽  
Expression Of Genes

Penicillium expansum is a major postharvest pathogen that mainly threatens the global pome fruit industry and causes great economic losses annually. In the present study, the antifungal effects and potential mechanism of cinnamon oil against P. expansum were investigated. Results indicated that 0.25 mg L−1 cinnamon oil could efficiently inhibit the spore germination, conidial production, mycelial accumulation, and expansion of P. expansum. In addition, it could effectively control blue mold rots induced by P. expansum in apples. Cinnamon oil could also reduce the expression of genes involved in patulin biosynthesis. Through a proteomic quantitative analysis, a total of 146 differentially expressed proteins (DEPs) involved in the carbohydrate metabolic process, most of which were down-regulated, were noticed for their large number and functional significance. Meanwhile, the expressions of 14 candidate genes corresponding to DEPs and the activities of six key regulatory enzymes (involving in cellulose hydrolyzation, Krebs circle, glycolysis, and pentose phosphate pathway) showed a similar trend in protein levels. In addition, extracellular carbohydrate consumption, intracellular carbohydrate accumulation, and ATP production of P. expansum under cinnamon oil stress were significantly decreased. Basing on the correlated and mutually authenticated results, we speculated that disturbing the fungal carbohydrate metabolic process would be partly responsible for the inhibitory effects of cinnamon oil on P. expansum growth. The findings would provide new insights into the antimicrobial mode of cinnamon oil.

scholarly journals Oxidative Stress Mediates the Fetal Programming of Hypertension by Glucocorticoids

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 531
Author(s):  
Jeremy Lamothe ◽  
Sandhya Khurana ◽  
Sujeenthar Tharmalingam ◽  
Chad Williamson ◽  
Collin J. Byrne ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Superoxide Dismutase ◽  
Fetal Programming ◽  
Cardiovascular Health ◽  
Phenylalanine Hydroxylase ◽  
Epigallocatechin Gallate ◽  
Female Offspring ◽  
Glutathione Peroxidase 1 ◽  
Protein Levels

The field of cardiovascular fetal programming has emphasized the importance of the uterine environment on postnatal cardiovascular health. Studies have linked increased fetal glucocorticoid exposure, either from exogenous sources (such as dexamethasone (Dex) injections), or from maternal stress, to the development of adult cardiovascular pathologies. Although the mechanisms are not fully understood, alterations in gene expression driven by altered oxidative stress and epigenetic pathways are implicated in glucocorticoid-mediated cardiovascular programming. Antioxidants, such as the naturally occurring polyphenol epigallocatechin gallate (EGCG), or the superoxide dismutase (SOD) 4-hydroxy-TEMPO (TEMPOL), have shown promise in the prevention of cardiovascular dysfunction and programming. This study investigated maternal antioxidant administration with EGCG or TEMPOL and their ability to attenuate the fetal programming of hypertension via Dex injections in WKY rats. Results from this study indicate that, while Dex-programming increased blood pressure in male and female adult offspring, administration of EGCG or TEMPOL via maternal drinking water attenuated Dex-programmed increases in blood pressure, as well as changes in adrenal mRNA and protein levels of catecholamine biosynthetic enzymes phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), in a sex-specific manner. Furthermore, programmed male offspring displayed reduced antioxidant glutathione peroxidase 1 (Gpx1) expression, increased superoxide dismutase 1 (SOD1) and catalase (CAT) expression, and increased pro-oxidant NADPH oxidase activator 1 (Noxa1) expression in the adrenal glands. In addition, prenatal Dex exposure alters expression of epigenetic regulators histone deacetylase (HDAC) 1, 5, 6, 7, 11, in male and HDAC7 in female offspring. These results suggest that glucocorticoids may mediate the fetal programming of hypertension via alteration of epigenetic machinery and oxidative stress pathways.

scholarly journals Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 229
Author(s):  
JunHyuk Woo ◽  
Hyesun Cho ◽  
YunHee Seol ◽  
Soon Ho Kim ◽  
Chanhyeok Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Computational Models ◽  
Neuronal Damage ◽  
Living Organism ◽  
The Body ◽  
Mitochondrial Functions ◽  
A Cell ◽  
The Brain ◽  
And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

scholarly journals An unusual thioredoxin system in the facultative parasite Acanthamoeba castellanii

2021 ◽  
Vol 78 (7) ◽  
pp. 3673-3689
Author(s):  
David Leitsch ◽  
Alvie Loufouma Mbouaka ◽  
Martina Köhsler ◽  
Norbert Müller ◽  
Julia Walochnik
Keyword(s):  
Oxidative Stress ◽  
Stop Codon ◽  
Acanthamoeba Castellanii ◽  
Methionine Sulfoxide ◽  
Redox System ◽  
Methionine Sulfoxide Reductase ◽  
Methionine Sulfoxide Reductase A ◽  
Protein Levels ◽  
Thioredoxin System ◽  
Facultative Parasite

AbstractThe free-living amoeba Acanthamoeba castellanii occurs worldwide in soil and water and feeds on bacteria and other microorganisms. It is, however, also a facultative parasite and can cause serious infections in humans. The annotated genome of A. castellanii (strain Neff) suggests the presence of two different thioredoxin reductases (TrxR), of which one is of the small bacterial type and the other of the large vertebrate type. This combination is highly unusual. Similar to vertebrate TrxRases, the gene coding for the large TrxR in A. castellanii contains a UGA stop codon at the C-terminal active site, suggesting the presence of selenocysteine. We characterized the thioredoxin system in A. castellanii in conjunction with glutathione reductase (GR), to obtain a more complete understanding of the redox system in A. castellanii and the roles of its components in the response to oxidative stress. Both TrxRases localize to the cytoplasm, whereas GR localizes to the cytoplasm and the large organelle fraction. We could only identify one thioredoxin (Trx-1) to be indeed reduced by one of the TrxRases, i.e., by the small TrxR. This thioredoxin, in turn, could reduce one of the two peroxiredoxins tested and also methionine sulfoxide reductase A (MsrA). Upon exposure to hydrogen peroxide and diamide, only the small TrxR was upregulated in expression at the mRNA and protein levels, but not the large TrxR. Our results show that the small TrxR is involved in the A. castellanii’s response to oxidative stress. The role of the large TrxR, however, remains elusive.

Sign in / Sign up

Export Citation Format

Share Document