scholarly journals Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate

2021 ◽  
Vol 22 (12) ◽  
pp. 6640
Author(s):  
Magdalena Cal ◽  
Irwin Matyjaszczyk ◽  
Karolina Filik ◽  
Rafał Ogórek ◽  
Young Ko ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Nuclear Dna ◽  
Colorimetric Assay ◽  
Eukaryotic Cell ◽  
Mitochondrial Activity ◽  
Ros Generation ◽  
Dependent Manner ◽  
Proper Functioning ◽  
The Many ◽  
First Time

3-bromopuryvate (3-BP) is a compound with unique antitumor activity. It has a selective action against tumor cells that exhibit the Warburg effect. It has been proven that the action of 3-BP is pleiotropic: it acts on proteins, glycolytic enzymes, reduces the amount of ATP, induces the formation of ROS (reactive oxygen species), and induces nuclear DNA damage. Mitochondria are important organelles for the proper functioning of the cell. The production of cellular energy (ATP), the proper functioning of the respiratory chain, or participation in the production of amino acids are one of the many functions of mitochondria. Here, for the first time, we show on the yeast model that 3-BP acts in the eukaryotic cell also by influence on mitochondria and that agents inhibiting mitochondrial function can potentially be used in cancer therapy with 3-BP. We show that cells with functional mitochondria are more resistant to 3-BP than rho0 cells. Using an MTT assay (a colorimetric assay for assessing cell metabolic activity), we demonstrated that 3-BP decreased mitochondrial activity in yeast in a dose-dependent manner. 3-BP induces mitochondrial-dependent ROS generation which results in ∆sod2, ∆por1, or ∆gpx1 mutant sensitivity to 3-BP. Probably due to ROS mtDNA lesions rise during 3-BP treatment. Our findings may have a significant impact on the therapy with 3-BP.

scholarly journals Cyclin D1 Determines Mitochondrial Function InVivo

2006 ◽  
Vol 26 (14) ◽  
pp. 5449-5469 ◽  
Author(s):  
Toshiyuki Sakamaki ◽  
Mathew C. Casimiro ◽  
Xiaoming Ju ◽  
Andrew A. Quong ◽  
Sanjay Katiyar ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Cyclin D1 ◽  
Mitochondrial Function ◽  
Nuclear Dna ◽  
Aerobic Glycolysis ◽  
Mammary Tumors ◽  
Regulatory Subunit ◽  
Mitochondrial Activity ◽  
Breast Cancers

ABSTRACT The cyclin D1 gene encodes a regulatory subunit of the holoenzyme that phosphorylates and inactivates the pRb tumor suppressor to promote nuclear DNA synthesis. cyclin D1 is overexpressed in human breast cancers and is sufficient for the development of murine mammary tumors. Herein, cyclin D1 is shown to perform a novel function, inhibiting mitochondrial function and size. Mitochondrial activity was enhanced by genetic deletion or antisense or small interfering RNA to cyclin D1. Global gene expression profiling and functional analysis of mammary epithelial cell-targeted cyclin D1 antisense transgenics demonstrated that cyclin D1 inhibits mitochondrial activity and aerobic glycolysis in vivo. Reciprocal regulation of these genes was observed in cyclin D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA synthesis and mitochondrial function.

scholarly journals Octadecaneuropeptide prevents toxicity induced by 6-hydroxydopamine in cultured rat astrocyte: involvement of the endogenous antioxidant systems and the intrinsic apoptotic pathway

2018 ◽  
Author(s):  
Hadhemi Kaddour ◽  
Yosra Hamdi ◽  
David Vaudry ◽  
Jérôme Leprince ◽  
Hubert Vaudry ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Antioxidant Systems ◽  
Mitochondrial Activity ◽  
Ros Generation ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Antioxidant Defences ◽  
Apoptotic Pathway

AbstractOxidative stress, associated with various neurodegenerative diseases, induces imbalance in ROS generation, impairs cellular antioxidant defences and finally triggers both neurons and astroglial cell death by apoptosis. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN). We have previously reported that ODN is a potent neuroprotective agent that prevents 6-OHDA-induced apoptotic neuronal death. The purpose of the present study was to investigate the potential glioprotective effect of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Incubation of astrocytes with graded concentrations of ODN (10−14 to 10−8 M) inhibited 6-OHDA-evoked cell death in a concentration- and time-dependent manner. In addition, ODN prevented the decrease of mitochondrial activity and caspase-3 activation induced by 6-OHDA. Toxin-treated cells exhibited high level of ROS associated with a generation of H2O2 and O2°-and a reduction of both SOD and catalase activities. Co-treatment of astrocytes with low concentrations of ODN dose dependently blocked 6-OHDA-evoked ROS production and inhibition of antioxidant enzymes activities. Taken together, these data demonstrate that ODN is a potent glioprotective agent that prevents 6-OHDA-induced oxidative stress and apoptotic cell death. ODN is thus a potential candidate to delay neuronal damages in various pathological conditions involving oxidative neurodegeneration.

scholarly journals Nuclear Receptor SHP, a Death Receptor That Targets Mitochondria, Induces Apoptosis and Inhibits Tumor Growth

2010 ◽  
Vol 30 (6) ◽  
pp. 1341-1356 ◽  
Author(s):  
Yuxia Zhang ◽  
Jamie Soto ◽  
Kyungtae Park ◽  
Gunda Viswanath ◽  
Scott Kuwada ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mitochondrial Function ◽  
Pancreatic Tumor ◽  
Death Receptor ◽  
Cellular Growth ◽  
Mitochondrial Activity ◽  
Apoptosis Inducer ◽  
Induction Of Apoptosis ◽  
First Time ◽  
Cell Death Receptor

ABSTRACT Small heterodimer partner (SHP) is an epigenetically regulated nuclear transcriptional repressor that suppresses the development of liver cancer by inhibiting cellular growth. Here we report a novel cytoplasmic function of SHP through its regulation of mitochondrial activity. SHP is a pivotal cell death receptor that targets mitochondria, where it binds with Bcl-2, disrupts Bcl-2/Bid interaction, and induces cytochrome c release. The apoptosis inducer AHPN {retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid} acts by regulating SHP gene expression and promotes the translocation of SHP from the nucleus to the mitochondria. Induction of apoptosis by SHP activation inhibits peritoneal pancreatic tumor growth. Our findings provide for the first time a mechanism by which SHP regulates cell survival, namely, by controlling mitochondrial function via modulating the activity of Bcl-2 through AHPN-mediated or AHPN-independent action. Thus, SHP regulates a mechanism by which apoptotic signals can mediate local control of mitochondrial function and apoptosis, which in turn may limit tumorigenesis.

scholarly journals AP39, a Mitochondria-Targeted Hydrogen Sulfide Donor, Supports Cellular Bioenergetics and Protects against Alzheimer’s Disease by Preserving Mitochondrial Function in APP/PS1 Mice and Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Feng-li Zhao ◽  
Fang Fang ◽  
Pei-feng Qiao ◽  
Ning Yan ◽  
Dan Gao ◽  
...  
Keyword(s):  
Cell Viability ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Drug Candidate ◽  
Mitochondrial Activity ◽  
Ros Generation ◽  
High Concentration ◽  
Low Concentrations ◽  
Mitochondrial Functions ◽  
Cellular Bioenergetics

Increasing evidence suggests that mitochondrial functions are altered in AD and play an important role in AD pathogenesis. It has been established that H2S homeostasis is balanced in AD. The emerging mitochondrial roles of H2S include antioxidation, antiapoptosis, and the modulation of cellular bioenergetics. Here, using primary neurons from the well-characterized APP/PS1 transgenic mouse model, we studied the effects of AP39 (a newly synthesized mitochondrially targeted H2S donor) on mitochondrial function. AP39 increased intracellular H2S levels, mainly in mitochondrial regions. AP39 exerted dose-dependent effects on mitochondrial activity in APP/PS1 neurons, including increased cellular bioenergy metabolism and cell viability at low concentrations (25–100 nM) and decreased energy production and cell viability at a high concentration (250 nM). Furthermore, AP39 (100 nM) increased ATP levels, protected mitochondrial DNA, and decreased ROS generation. AP39 regulated mitochondrial dynamics, shifting from fission toward fusion. After 6 weeks, AP39 administration to APP/PS1 mice significantly ameliorated their spatial memory deficits in the Morris water maze and NORT and reduced Aβdeposition in their brains. Additionally, AP39 inhibited brain atrophy in APP/PS1 mice. Based on these results, AP39 was proposed as a promising drug candidate for AD treatment, and its anti-AD mechanism may involve protection against mitochondrial damage.

scholarly journals Simple, reliable, and time-efficient colorimetric method for the assessment of mitochondrial function and toxicity

2018 ◽  
Vol 18 (4) ◽  
pp. 367-374 ◽  
Author(s):  
Faraz Ahmad ◽  
Widyan Alamoudi ◽  
Shafiul Haque ◽  
Mohammad Salahuddin ◽  
Khaldoon Alsamman
Keyword(s):  
Mitochondrial Function ◽  
Colorimetric Assay ◽  
Colorimetric Method ◽  
Mitochondrial Activity ◽  
Blue Color ◽  
Energy Regulation ◽  
Disease States ◽  
Wide Range ◽  
Cost Efficient

Mitochondria are organelles involved in the production of cellular energy, regulation of Ca2+ and redox signaling, and are critical for normal functioning of eukaryotic cells. The dysfunction of mitochondria has been implicated in a wide range of diseases, including metabolic and neurodegenerative disorders and different types of cancers. To better understand the role of mitochondria in healthy and disease states, the development of efficient and reliable tools for the assessment of mitochondrial function is particularly important. Janus green B (JG-B) is a supravital lipophilic cationic dye which, in its oxidized form, has a green-blue color. As JG-B is taken up and reduced by metabolically active mitochondria, the dye has been used for assessing the purity, integrity and metabolic activity of mitochondria with microscopy-based methods. Here we present a simple, time- and cost-efficient JG-B-based colorimetric assay for assessing mitochondrial function, activity and toxicity. The method is based upon reduction of JG-B by mitochondrial dehydrogenases to diethylsafranine, which is pink colored and has a maximum absorption at 550 nm. In this proof of principle study, using in vitro mitochondrial preparations isolated from rat brain, we provide evidence that monitoring JG-B conversion to diethylsafranine can be used as a reliable and robust indicator of mitochondrial activity and toxicity. Because of its simplicity and efficiency in terms of costs and time, this assay has a wide potential in analytical as well as therapeutic areas of biomedical research.

Unrivalled Influence

2013 ◽  
Author(s):  
Judith Herrin
Keyword(s):  
Political Life ◽  
General Introduction ◽  
Women And Gender ◽  
Mothers And Daughters ◽  
Diverse Range ◽  
Long Span ◽  
Imperial Court ◽  
And Gender ◽  
The Many ◽  
First Time

This book explores the exceptional roles that women played in the vibrant cultural and political life of medieval Byzantium. This book evokes the complex and exotic world of Byzantium's women, from empresses and saints to uneducated rural widows. Drawing on a diverse range of sources, the book sheds light on the importance of marriage in imperial statecraft, the tense coexistence of empresses in the imperial court, and the critical relationships of mothers and daughters. It looks at women's interactions with eunuchs, the in-between gender in Byzantine society, and shows how women defended their rights to hold land. The book describes how women controlled their inheritances, participated in urban crowds demanding the dismissal of corrupt officials, followed the processions of holy icons and relics, and marked religious feasts with liturgical celebrations, market activity, and holiday pleasures. The vivid portraits that emerge here reveal how women exerted an unrivalled influence on the patriarchal society of Byzantium, and remained active participants in the many changes that occurred throughout the empire's millennial history. The book brings together the author's finest essays on women and gender written throughout the long span of her career. This volume includes three new essays published here for the very first time and a new general introduction. It also provides a concise introduction to each essay that describes how it came to be written and how it fits into her broader views about women and Byzantium.

scholarly journals The synergistic interference effect of silica nanoparticles concentration and the wavelength of ELISA on the colorimetric assay of cell toxicity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Abbasi ◽  
Hassan Hashemi ◽  
Mohammad Reza Samaei ◽  
Amir SavarDashtaki ◽  
Abooalfazl Azhdarpoor ◽  
...  
Keyword(s):  
Mtt Assay ◽  
Interference Effect ◽  
Polynomial Regression ◽  
Colorimetric Assay ◽  
Synergistic Effects ◽  
Cell Toxicity ◽  
Diphenyltetrazolium Bromide ◽  
Nanoparticles Concentration ◽  
Artificial Neural Network Ann ◽  
First Time

AbstractThe 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is the most common method for the determination of cell toxicity, but some factors limit the sensitivity of this method, such as pH. Less attention had been paid to the interference effect of optical and plasmonic properties of SiO2 nanoparticles (NPs) in the wavelength range assigned to MTT. This study investigated the synergistic interference effect of SiO2 NPs and wavelength on MTT assay for the first time. The examined variables included the type of SiO2 NPs concentrations (1, 10, and 100 mM) and different wavelengths (470, 490, 520, and 570 nm). The results showed that optical density (OD) increased (p < 0.05) when wavelength and the concentration of crystalline SiO2 NPs increased. So, the maximum OD at 10 and 100 mM were attributed to crystalline SiO2 NPs (p < 0.05) due to the functional group, whereas it was related to amorphous at 1 mM (p > 0.05). According to polynomial regression modeling (PRM), the maximum interference effect was predicted at crystalline SiO2 NPs and wavelength > 550 nm. Besides, the synergistic effects of SiO2 NPs, wavelength, and concentration of NPs had been a good fitting with first-order PRM. Thus, the concentration of SiO2 NPs had a confounder factor in colorimetric for MTT assay. The best artificial neural network (ANN) structure was related to the 3:7:1 network (Rall = 0.936, MSE = 0.0006, MAPE = 0.063). The correlation between the actual and predicted data was 0.88. As SiO2 NPs presence is an interfering factor in MTT assay concerning wavelength, it is suggested wavelength use with minimum confounding effect for MTT assay.

scholarly journals Fe3O4@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tong Chen ◽  
Qiang Chu ◽  
Mengyang Li ◽  
Gaorong Han ◽  
Xiang Li
Keyword(s):  
Fenton Reaction ◽  
Pt Nanoparticles ◽  
Therapeutic Modality ◽  
Ros Generation ◽  
Tumor Treatment ◽  
Superior Efficacy ◽  
Platinum Nanocrystals ◽  
First Time

AbstractElectrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O4@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe3O4@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H2O2 into ROS via Fenton reaction. In addition, Fe3+ ions released from Fe3O4@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Brassinolide Enhances the Level of Brassinosteroids, Protein, Pigments, and Monosaccharides in Wolffia arrhiza Treated with Brassinazole

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1311
Author(s):  
Magdalena Chmur ◽  
Andrzej Bajguz
Keyword(s):  
Plant Growth ◽  
Growth And Development ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Plant Growth And Development ◽  
Concentration Dependent Manner ◽  
Spectrophotometric Methods ◽  
Synthetic Inhibitor ◽  
Wolffia Arrhiza ◽  
First Time

Brassinolide (BL) represents brassinosteroids (BRs)—a group of phytohormones that are essential for plant growth and development. Brassinazole (Brz) is as a synthetic inhibitor of BRs’ biosynthesis. In the present study, the responses of Wolffia arrhiza to the treatment with BL, Brz, and the combination of BL with Brz were analyzed. The analysis of BRs and Brz was performed using LC-MS/MS. The photosynthetic pigments (chlorophylls, carotenes, and xanthophylls) levels were determined using HPLC, but protein and monosaccharides level using spectrophotometric methods. The obtained results indicated that BL and Brz influence W. arrhiza cultures in a concentration-dependent manner. The most stimulatory effects on the growth, level of BRs (BL, 24-epibrassinolide, 28-homobrassinolide, 28-norbrassinolide, catasterone, castasterone, 24-epicastasterone, typhasterol, and 6-deoxytyphasterol), and the content of pigments, protein, and monosaccharides, were observed in plants treated with 0.1 µM BL. Whereas the application of 1 µM and 10 µM Brz caused a significant decrease in duckweed weight and level of targeted compounds. Application of BL caused the mitigation of the Brz inhibitory effect and enhanced the BR level in duckweed treated with Brz. The level of BRs was reported for the first time in duckweed treated with BL and/or Brz.

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