scholarly journals Overexpression of Neuroglobin Promotes Energy Metabolism and Autophagy Induction in Human Neuroblastoma SH-SY5Y Cells

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3394
Author(s):  
Valeria Manganelli ◽  
Illari Salvatori ◽  
Michele Costanzo ◽  
Antonella Capozzi ◽  
Daniela Caissutti ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Atp Production ◽  
Cellular Processes ◽  
Proteomic Approach ◽  
Autophagy Induction ◽  
Bioenergetic Metabolism ◽  
Response To Stress

Neuroglobin (NGB) is an O2-binding globin mainly expressed in the central and peripheral nervous systems and cerebrospinal fluid. Previously, it was demonstrated that NGB overexpression protects cells from hypoxia-induced death. To investigate processes promoted by NGB overexpression, we used a cellular model of neuroblastoma stably overexpressing an NGB-FLAG construct. We used a proteomic approach to identify the specific profile following NGB overexpression. To evaluate the role of NGB overexpression in increasing energetic metabolism, we measured oxygen consumption rate (OCR) and the extracellular acidification rate through Seahorse XF technology. The effect on autophagy induction was evaluated by analyzing SQSTM1/p62 and LC3-II expression. Proteomic analysis revealed several differentially regulated proteins, involved in oxidative phosphorylation and integral mitochondrial proteins linked to energy metabolism. The analysis of mitochondrial metabolism demonstrated that NGB overexpression increases mitochondrial ATP production. Indeed, NGB overexpression enhances bioenergetic metabolism, increasing OCR and oxygen consumption. Analysis of autophagy induction revealed an increase of LC3-II together with a significant decrease of SQSTM1/p62, and NGB-LC3-II association during autophagosome formation. These results highlight the active participation of NGB in several cellular processes that can be upregulated in response to NGB overexpression, playing a role in the adaptive response to stress in neuroblastoma cells.

Evolutionary Consequences of Tradeoffs between Yield and Rate of ATP Production

2002 ◽  
Vol 216 (1) ◽  
Author(s):  
Thomas Pfeiffer ◽  
Sebastian Bonhoeffer
Keyword(s):  
Game Theory ◽  
Population Dynamics ◽  
Energy Metabolism ◽  
Adenosine Triphosphate ◽  
Organic Material ◽  
High Yield ◽  
Atp Production ◽  
Cellular Processes ◽  
Quantitative Properties ◽  
Evolutionary Consequences

Adenosine triphosphate (ATP) is a key compound in the energy metabolism of cells and is required to drive vital biochemical reactions. In heterotrophic organisms ATP production is coupled to the degradation of energy-rich organic material taken up from the environment. In the transfer of the environmental energy to cellular processes heterotrophs face a tradeoff, since the conversion of the environmental energy into ATP cannot be both maximally fast and efficient. Here we show how tradeoffs between rate and yield of ATP production arise firstly from thermodynamical principles, and secondly for the ATP production by respiration and fermentation. Using methods derived from game theory and population dynamics we investigate the evolutionary consequences for both tradeoffs. We show that spatially structured environments enable the evolution of efficient pathways with high yield. The strategies of ATP production realized in a population, however, depend on the quantitative properties of the tradeoffs.

scholarly journals Energy Metabolism Disturbances in Cell Models of PARK2 CNV Carriers with ADHD

2020 ◽  
Vol 9 (12) ◽  
pp. 4092
Author(s):  
Viola Stella Palladino ◽  
Andreas G. Chiocchetti ◽  
Lukas Frank ◽  
Denise Haslinger ◽  
Rhiannon McNeill ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Mitochondrial Dynamics ◽  
Control Cell ◽  
Copy Number Variants ◽  
Atp Production ◽  
Cellular Models ◽  
Gene And Protein Expression ◽  
Consumption Rates ◽  
Cellular Phenotypes

The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.

scholarly journals 6-Hydroxydopamine Induce Neurodegeneration In Terminally Differentiated SH-SY5Y Neuroblastoma Cells Via Enrichment Of The Nucleosomal Degradation Pathway: A Global Proteomic Approach

2021 ◽  
Author(s):  
Kasthuri Bai Magalingam ◽  
Sushela Devi Somanath ◽  
Premdass Ramdas ◽  
Nagaraja Haleagrahara ◽  
Ammu Kutty Radhakrishnan
Keyword(s):  
Lupus Erythematosus ◽  
Ribosomal Proteins ◽  
Molecular Mechanisms ◽  
Cell Model ◽  
Neuroblastoma Cells ◽  
Neural Cells ◽  
Down Regulation ◽  
Human Neuroblastoma ◽  
Proteomic Approach ◽  
6 Hydroxydopamine

Abstract The SH-SY5Y human neuroblastoma cells have been used for decades as an in vitro cell model of dopaminergic neurons to explore the underlying science of cellular and molecular mechanisms of neurodegeneration in Parkinson’s disease (PD). However, data revealing the protein expression changes in 6-OHDA induced cytotoxicity in differentiated SH-SY5Y cells remain void. Therefore, we investigated the differentially regulated proteins expressed in terminally differentiated SH-SY5Y cells (differ-SH-SY5Y neural cells) exposed to 6-hydroxydopamine (6-OHDA) using the LC-MS/MS technology and interpreted the data using the online bioinformatics databases such as PANTHER, STRING, and KEGG. Our studies demonstrated the neuronal development in differ-SH-SY5Y neural cells was implicated by the overexpression of proteins responsible for neurite formations such as calnexin (CANX) and calreticulin (CALR) besides significant down-regulation of ribosomal proteins. The enrichment of the KEGG ribosome pathway was detected with significant down-regulation (p < 0.05) of all the 21 ribosomal proteins in differ-SH-SY5Y neural cells compared with undifferentiated cells. Whereas in the PD model, the pathological changes induced by 6-OHDA were indicated by the presence of unfolded and misfolded proteins, which triggered the response of 10 kDa heat shock proteins, namely HSPE1 and HSPA9. Moreover, the 6-OHDA induced neurodegeneration in differ-SH-SY5Y neural cells also upregulated the voltage-dependent anion-selective channel protein 1 (VDAC1) protein and enriched the KEGG systemic lupus erythematosus pathway that was regulated by all 17 histone proteins (p < 0.05) in differ-SH-SY5Y neural cells. These results suggest the central event in the neurodegenerative mechanism induced by 6-OHDA in the PD cell model was the nucleosomal degradation in the KEGG-SLE pathway indicated by the increased histone release in the apoptotic cells.

scholarly journals Variation in the link between oxygen consumption and ATP production, and its relevance for animal performance

2015 ◽  
Vol 282 (1812) ◽  
pp. 20151028 ◽  
Author(s):  
Karine Salin ◽  
Sonya K. Auer ◽  
Benjamin Rey ◽  
Colin Selman ◽  
Neil B. Metcalfe
Keyword(s):  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Reproductive Output ◽  
Evolutionary Ecology ◽  
Environmental Parameters ◽  
Animal Performance ◽  
Atp Production ◽  
Cellular Energy ◽  
Mitochondrial Efficiency ◽  
The Relationship

It is often assumed that an animal's metabolic rate can be estimated through measuring the whole-organism oxygen consumption rate. However, oxygen consumption alone is unlikely to be a sufficient marker of energy metabolism in many situations. This is due to the inherent variability in the link between oxidation and phosphorylation; that is, the amount of adenosine triphosphate (ATP) generated per molecule of oxygen consumed by mitochondria (P/O ratio). In this article, we describe how the P/O ratio can vary within and among individuals, and in response to a number of environmental parameters, including diet and temperature. As the P/O ratio affects the efficiency of cellular energy production, its variability may have significant consequences for animal performance, such as growth rate and reproductive output. We explore the adaptive significance of such variability and hypothesize that while a reduction in the P/O ratio is energetically costly, it may be associated with advantages in terms of somatic maintenance through reduced production of reactive oxygen species. Finally, we discuss how considering variation in mitochondrial efficiency, together with whole-organism oxygen consumption, can permit a better understanding of the relationship between energy metabolism and life history for studies in evolutionary ecology.

scholarly journals Laboratory Yeast Strains Rely On Oxidative Phosphorylation For Efficient ATP Production

2021 ◽  
Author(s):  
Akshay Moharir ◽  
Lincoln Gay ◽  
Markus Babst
Keyword(s):  
Plasma Membrane ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
High Glucose ◽  
Anaerobic Conditions ◽  
Atp Production ◽  
Yeast Strains ◽  
Biological Studies

AbstractEven though it is a well-accepted fact that the energy metabolism of yeast is likely to impact all cellular activities, surprising little is known about the ATP homeostasis of particular yeast strains that are commonly used in cell biological studies. Therefore, we determined key parameters such as oxygen consumption and fermentation rates of the lab strain SEY6210. Our data indicated that even at high glucose concentrations, SEY6210 produces 30-50% of cellular ATP from oxidative phosphorylation. Loss of respiration, either by disrupting ATP synthase function or by growth in anaerobic conditions, was not fully compensated by fermentation and as a result affected energy intensive processes such as the maintenance of the plasma membrane proton gradient and the associated import of nutrients.

p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
Author(s):  
İrem Bozbey ◽  
Suat Sari ◽  
Emine Şalva ◽  
Didem Kart ◽  
Arzu Karakurt
Keyword(s):  
Molecular Modeling ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Cytotoxic Agents ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Modeling Studies ◽  
Broth Microdilution Method ◽  
Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

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