scholarly journals Caffeoylquinic Acid Derivatives of Purple Sweet Potato as Modulators of Mitochondrial Function in Mouse Primary Hepatocytes

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 319
Author(s):  
Andrea Torres ◽  
Lilia G. Noriega ◽  
Claudia Delgadillo-Puga ◽  
Armando R. Tovar ◽  
Arturo Navarro-Ocaña
Keyword(s):  
Sweet Potato ◽  
Mitochondrial Function ◽  
Energy Demand ◽  
Antioxidant Properties ◽  
Mitochondrial Activity ◽  
Primary Hepatocytes ◽  
Caffeoylquinic Acid ◽  
Hepatic Cells ◽  
Purple Sweet Potato ◽  
The Impact

Owing to their antioxidant properties, caffeoylquinic acid (CQA)-derivatives could potentially improve the impaired metabolism in hepatic cells, however, their effect on mitochondrial function has not been demonstrated yet. Here, we evaluated the impact of three CQA-derivatives extracted from purple sweet potato, namely 5-CQA, 3,4- and 4,5-diCQA, on mitochondrial activity in primary hepatocytes using an extracellular flux analyzer. Notably, an increase of maximal respiration and spare respiratory capacity were observed when 5-CQA and 3,4-diCQA were added to the system indicating the improved mitochondrial function. Moreover, 3,4-diCQA was shown to considerably increase glycolytic reserve which is a measure of cell capability to respond to an energy demand through glycolysis. Conversely, 4,5-diCQA did not modify mitochondrial activity but increased glycolysis at low concentration in primary hepatocytes. All compounds tested improved cellular capacity to oxidize fatty acids. Overall, our results demonstrated the potential of test CQA-derivatives to modify mitochondrial function in hepatic cells. It is especially relevant in case of dysfunctional mitochondria in hepatocytes linked to hepatic steatosis during obesity, diabetes, and metabolic syndrome.

scholarly journals Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bethany Muller ◽  
Niamh Lewis ◽  
Tope Adeniyi ◽  
Henry J. Leese ◽  
Daniel R. Brison ◽  
...  
Keyword(s):  
Real Time ◽  
Oocyte Maturation ◽  
Small Groups ◽  
Mitochondrial Function ◽  
Mitochondrial Activity ◽  
Flux Analysis ◽  
Mammalian Oocyte ◽  
Extracellular Flux ◽  
Early Embryos ◽  
The Impact

AbstractMitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific molecular events remains lacking. Here, extracellular flux analysis (EFA) was applied to small groups of bovine, equine, mouse and human oocytes and bovine early embryos to measure OCR and its components. Using EFA, we report the changes in mitochondrial activity during the processes of oocyte maturation, fertilisation, and pre-implantation development to blastocyst stage in response to physiological demands in mammalian embryos. Crucially, we describe the real time partitioning of overall OCR to spare capacity, proton leak, non-mitochondrial and coupled respiration – showing that while activity changes over the course of development in response to physiological demand, the overall efficiency is unchanged. EFA is shown to be able to measure mitochondrial function in small groups of mammalian oocytes and embryos in a manner which is robust, rapid and easy to use. EFA is non-invasive and allows real-time determination of the impact of compounds on OCR, facilitating an assessment of the components of mitochondrial activity. This provides proof-of-concept for EFA as an accessible system with which to study mammalian oocyte and embryo metabolism.

Interferon-beta affects mitochondrial activity in CD4+lymphocytes: Implications for mechanism of action in multiple sclerosis

2014 ◽  
Vol 21 (10) ◽  
pp. 1262-1270 ◽  
Author(s):  
Aiden Haghikia ◽  
Simon Faissner ◽  
Derek Pappas ◽  
Bartosz Pula ◽  
Denis A Akkad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Energy Metabolism ◽  
Mitochondrial Function ◽  
Interferon Beta ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Mitochondrial Activity ◽  
Mitochondrial Energy Metabolism ◽  
The Impact

Background:Whereas cellular immune function depends on energy supply and mitochondrial function, little is known on the impact of immunotherapies on cellular energy metabolism.Objective:The objective of this paper is to assess the effects of interferon-beta (IFN-β) on mitochondrial function of CD4+T cells.Methods:Intracellular adenosine triphosphate (iATP) in phytohemagglutinin (PHA)-stimulated CD4+cells of multiple sclerosis (MS) patients treated with IFN-β and controls were analyzed in a luciferase-based assay. Mitochondrial-transmembrane potential (ΔΨm) in IFN-β-treated peripheral blood mononuclear cells (PBMCs) was investigated by flow cytometry. Expression of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) in CD4+cells of IFN-β-treated individuals and correlations between genetic variants in the key metabolism regulator PGC-1α and IFN-β response in MS were analyzed.Results:IFN-β-treated MS patients exhibited a dose-dependent reduction of iATP levels in CD4+T cells compared to controls ( p < 0.001). Mitochondrial effects were reflected by depolarization of ΔΨm. Expression data revealed changes in the transcription of OXPHOS-genes. iATP levels in IFN-β-responders were reduced compared to non-responders ( p < 0.05), and the major T allele of the SNP rs7665116 of PGC-1α correlated with iATP-levels.Conclusion:Reduced iATP-synthesis ex vivo and differential expression of OXPHOS-genes in CD4+T cells point to unknown IFN-β effects on mitochondrial energy metabolism, adding to potential pleiotropic mechanisms of action.

scholarly journals The Acute Extracellular Flux (XF) Assay to Assess Compound Effects on Mitochondrial Function

2014 ◽  
Vol 20 (3) ◽  
pp. 422-429 ◽  
Author(s):  
Ruolan Wang ◽  
Steven J. Novick ◽  
James B. Mangum ◽  
Kennedy Queen ◽  
David A. Ferrick ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Activity ◽  
Screening Methods ◽  
Drug Induced ◽  
Whole Cells ◽  
Drug Candidates ◽  
Adverse Health Outcomes ◽  
Extracellular Flux ◽  
Screening Platform ◽  
The Impact

Numerous investigations have linked mitochondrial dysfunction to adverse health outcomes and drug-induced toxicity. The pharmaceutical industry is challenged with identifying mitochondrial liabilities earlier in drug development and thereby reducing late-stage attrition. Consequently, there is a demand for reliable, higher-throughput screening methods for assessing the impact of drug candidates on mitochondrial function. The extracellular flux (XF) assay described here is a plate-based method in which galactose-conditioned HepG2 cells were acutely exposed to test compounds, then real-time changes in the oxygen consumption rate and extracellular acidification rate were simultaneously measured using a Seahorse Bioscience XF-96 analyzer. The acute XF assay was validated using marketed drugs known to modulate mitochondrial function, and data analysis was automated using a spline curve fitting model developed at GlaxoSmithKline. We demonstrate that the acute XF assay is a robust, sensitive screening platform for evaluating drug-induced effects on mitochondrial activity in whole cells.

scholarly journals How Pullulanase Affects Resistant Starch and Antioxidant Activity in Purple Sweet Potato Powder?

2019 ◽  
Vol 7 (11) ◽  
pp. 1795
Author(s):  
Gita Nevara Addelia ◽  
Shyan Yea Chay ◽  
Kharidah Muhammad ◽  
Hasanah Mohd Ghazali ◽  
Roselina Karim
Keyword(s):  
Sweet Potato ◽  
Resistant Starch ◽  
Radical Scavenging Activity ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Anthocyanin Content ◽  
Total Anthocyanin ◽  
Plant Powders ◽  
Potato Powder ◽  
Purple Sweet Potato

Purple sweet potato (PSP) serves as a potential source for dual functionalities of resistant starch (RS) and antioxidants. This study aims to evaluate the effects of pullulanase enzyme on these functionalities. Results showed that the incorporation of pullulanase into PSP powder could significantly increase the RS content from 3.06 g/100g to 7.11 g/100g. However, total anthocyanin content and DPPH radical scavenging activity reduced significantly, due to the interference from RS fragments on anthocyanins. Securing both functionalities (RS and antioxidant) within the same sample is seemingly impossible. A compromise between RS and antioxidant properties in coloured, starchy plant powders is recommended.

scholarly journals Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos

2019 ◽  
Author(s):  
Bethany Muller ◽  
Niamh Lewis ◽  
Tope Adeniyi ◽  
Henry J Leese ◽  
Daniel Brison ◽  
...  
Keyword(s):  
Real Time ◽  
Oocyte Maturation ◽  
Small Groups ◽  
Mitochondrial Function ◽  
Mitochondrial Activity ◽  
Flux Analysis ◽  
Spare Capacity ◽  
Extracellular Flux ◽  
Early Embryos ◽  
The Impact

1.AbstractBackgroundMitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific molecular events remains lacking.ResultsHere, extracellular flux analysis (EFA) was applied to small groups of bovine, equine, mouse and human oocytes and bovine early embryos to measure OCR. Using EFA, we report the changes in mitochondrial activity during the processes of oocyte maturation, fertilization, and pre-implantation development to blastocyst stage in response to physiological demands in mammalian embryos. Crucially, we describe the real time partitioning of overall OCR to spare capacity, proton leak, non-mitochondrial and coupled respiration – showing that while there are alterations in activity over the course of development to respond to physiological demand, the overall efficiency is unchanged.ConclusionEFA is shown to be able to measure mitochondrial function in small groups of mammalian oocytes and embryos in a manner which is robust, rapid and easy to use. EFA is non-invasive and allows real-time determination of the impact of compounds on OCR, facilitating an assessment of the parameters of mitochondrial activity. This provides proof-of-concept for EFA as an accessible system with which to study oocyte and embryo metabolism.

scholarly journals An Autosomal Dominant Form of Ras-Related C3 Botulinum Toxin Substrate 2 (RAC2) Is Associated with Haematopoiesis Failure

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4306-4306
Author(s):  
Chantal Lagresle-Peyrou ◽  
Aurélien Olichon ◽  
Hanem Sadek ◽  
Philippe Roche ◽  
Claudine Tardy ◽  
...  
Keyword(s):  
Energy Demand ◽  
Clinical Phenotype ◽  
Severe Combined Immunodeficiency ◽  
Mitochondrial Protein ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Mitochondrial Activity ◽  
Hematopoietic Stem ◽  
Screening Programs ◽  
The Impact

Abstract Severe combined immunodeficiencies (SCIDs) constitute a heterogeneous group of life-threatening genetic disorders that typically present in the first year of life. Reticular dysgenesis (RD) is an autosomal recessive form of human Severe Combined Immunodeficiency (SCIDs) characterized by the absence of blood neutrophils and T lymphocytes. This pathology is due to biallelic mutations in the adenylate kinase 2 (AK2) gene, encoding for a mitochondrial protein which regulates the homeostasis of adenine nucleotides. In three newborns presenting a RD-like clinical phenotype as frequent infections and a profound leukopenia, we identified an heterozygous dominant missense mutation in the gene coding for Rac Family Small GTPase 2 (RAC2) protein (p.G12R). Hematopoietic stem cell transplantation (HSCT) performed soon after birth was successful in two out of the three patients attesting that the inherited defect was intrinsic and not micro-environmental. RAC2 protein belongs to the Rac subfamily of RHO small GTPases. In the inactive GDP-bound state, RAC2 is located in the cytosol and upon stimulation, the active RAC2-GTP-bound form translocates to the plasma membrane. Unlike the other members of the Rac subfamily (RAC1 and RAC3), RAC2 is mostly expressed on hematopoietic cells and during T cell differentiation. To gain insight into the disease, we transduced human hematopoietic stem and progenitor cells (HSPCs) with a lentiviral construct containing the RAC2 mutated form. The mutation inhibits HSPCs proliferation and differentiation toward the myeloid and lymphoid lineages reproducing the patients' clinical phenotype. In this condition, we also observed high apoptosis level and an alteration of mitochondrial activity and Ros production. In a biochemical model, we demonstrated that the substitution of the glycine (G) amino-acid by a bulky flexible arginine (R) may prevent GTP hydrolysis. Lastly, our findings suggest that RAC2 gene sequencing must be considered in newborn screening programs for SCID detection. To decipher the mechanisms regulating RAC2 functions, we studied the impact of the p.G12R mutation on a human AML cell line expressing RAC2 protein. Our preliminary data highlight that the cell cycle and mitochondrial activity are disrupted by G12R mutation. By holotomography, we also observed morphological changes and accumulation of lipid droplets into the cells. All these data suggest that RAC2 defective signalling pathway is linked to cell metabolism imbalance and further investigations are ongoing to better understand how RAC2 controls cell energy demand, especially during differentiation. Disclosures Cavazzana: Smart Immune: Other: co-founder.

Interaction of Purple Sweet Potato Extract with Ascorbic Acid in FeCl3 Solution

2014 ◽  
Vol 680 ◽  
pp. 32-37
Author(s):  
Ayende ◽  
Andi Rustandi ◽  
Johny Wahyuadi Soedarsono ◽  
Dedi Priadi ◽  
Sulistijono ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Corrosion Inhibitor ◽  
Sweet Potato ◽  
Inhibition Efficiency ◽  
Antioxidant Properties ◽  
Enzymatic Reaction ◽  
Iron Chelate ◽  
Green Corrosion Inhibitor ◽  
Potato Extract ◽  
Purple Sweet Potato

Utilization of ascorbic acid as corrosion inhibitor has several weaknesses. These weaknesses are easy to oxidize in solution form and reduction of its antioxidant properties due to heat, light, oxidizing agent, dissolve oxygen, and heavy metals. Purple sweet potato extract is an alternative green corrosion inhibitor with major contains of anthocyanin compound. Anthocyanin will withstand enzymatic reaction and oxidation process of ascorbic acid. Addition of purple sweet potato extract in ascorbic acid will enhance inhibition efficiency of steel compare to the used of ascorbic acid alone. Interaction of purple sweet potato extract with 0.01M ascorbic acid in 0.1M FeCl3environment was analyzed using FTIR spectroscopy. The result shows that interaction of purple sweet potato extract with ascorbic acid in 0.1M FeCl3build ability to form iron chelate.

scholarly journals The Role of Mitochondrial Calcium Homeostasis in Alzheimer’s and Related Diseases

2020 ◽  
Vol 21 (23) ◽  
pp. 9153
Author(s):  
Kerry C. Ryan ◽  
Zahra Ashkavand ◽  
Kenneth R. Norman
Keyword(s):  
Neurodegenerative Diseases ◽  
Calcium Signaling ◽  
Mitochondrial Function ◽  
Reciprocal Relationship ◽  
Mitochondrial Activity ◽  
Mitochondrial Calcium ◽  
Protein Homeostasis ◽  
Neuronal Function ◽  
The Impact

Calcium signaling is essential for neuronal function, and its dysregulation has been implicated across neurodegenerative diseases, including Alzheimer’s disease (AD). A close reciprocal relationship exists between calcium signaling and mitochondrial function. Growing evidence in a variety of AD models indicates that calcium dyshomeostasis drastically alters mitochondrial activity which, in turn, drives neurodegeneration. This review discusses the potential pathogenic mechanisms by which calcium impairs mitochondrial function in AD, focusing on the impact of calcium in endoplasmic reticulum (ER)–mitochondrial communication, mitochondrial transport, oxidative stress, and protein homeostasis. This review also summarizes recent data that highlight the need for exploring the mechanisms underlying calcium-mediated mitochondrial dysfunction while suggesting potential targets for modulating mitochondrial calcium levels to treat neurodegenerative diseases such as AD.

scholarly journals The Potential Role of Polyphenols in Modulating Mitochondrial Bioenergetics within the Skeletal Muscle: A Systematic Review of Preclinical Models

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2791
Author(s):  
Sinenhlanhla X. H. Mthembu ◽  
Phiwayinkosi V. Dludla ◽  
Khanyisani Ziqubu ◽  
Tawanda M. Nyambuya ◽  
Abidemi P. Kappo ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Antioxidant Properties ◽  
General Interest ◽  
Mitochondrial Bioenergetics ◽  
Metabolic Function ◽  
Preclinical Models ◽  
Metabolic Complications ◽  
The Impact

Polyphenols are naturally derived compounds that are increasingly being explored for their various health benefits. In fact, foods that are rich in polyphenols have become an attractive source of nutrition and a potential therapeutic strategy to alleviate the untoward effects of metabolic disorders. The last decade has seen a rapid increase in studies reporting on the bioactive properties of polyphenols against metabolic complications, especially in preclinical models. Various experimental models involving cell cultures exposed to lipid overload and rodents on high fat diet have been used to investigate the ameliorative effects of various polyphenols against metabolic anomalies. Here, we systematically searched and included literature reporting on the impact of polyphenols against metabolic function, particularly through the modulation of mitochondrial bioenergetics within the skeletal muscle. This is of interest since the skeletal muscle is rich in mitochondria and remains one of the main sites of energy homeostasis. Notably, increased substrate availability is consistent with impaired mitochondrial function and enhanced oxidative stress in preclinical models of metabolic disease. This explains the general interest in exploring the antioxidant properties of polyphenols and their ability to improve mitochondrial function. The current review aimed at understanding how these compounds modulate mitochondrial bioenergetics to improve metabolic function in preclinical models on metabolic disease.

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