scholarly journals Curcumae Radix Extract Reduces Beta-Amyloid (Αβ) and Tau Protein Through Increased Mitochondrial Respiration

2021 ◽  
Author(s):  
Seong lae Jo ◽  
Hyun Yang ◽  
Jun H. Heo ◽  
Sang R. Lee ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Respiration ◽  
Metabolic Flux ◽  
Tca Cycle ◽  
Basal Respiration ◽  
Atp Production ◽  
Inflammatory Conditions ◽  
Brain Tumor Cells

Abstract Background: Neurodegenerative diseases are increasingly being studied owing to the increasing proportion of the aging population. Several potential compounds have been studied to prevent neurodegenerative diseases, one of which is Curcumae Radix that is known to be beneficial for inflammatory conditions, metabolic syndrome, and various types of pain. However, it is not well studied and its influence on energy metabolism in neurodegenerative diseases is unclear. We focused on the relationship between neurodegenerative diseases and energy metabolism through Curcumae Radix extract in an animal model. Methods: Mice were treated with Curcumae Radix extract for 5 weeks orally 5 times in a week (50 mg/kg body weight). Murine delayed brain tumor (DBT) cells were supplemented with Curcumae Radix extract. We monitored the neurodegenerative makers and metabolic indicators using Western blotting and qRT-PCR and then assessed the cellular glycolysis and mitochondrial respiration through metabolic flux assay.Results: Low expression levels of Alzheimer’s disease-related markers were observed after treatment with Curcumae Radix extract. It was determined through the pAMPK/AMPK ratio that the ATP state was sufficient in the cerebrum and brain tumor cells. With this, an increase in glycolysis would be expected as glucose is the main energy source of the brain. However, glycolysis-related genes and the extracellular acidification rate showed that glycolysis decreased. Despite this, basal respiration and ATP production through mitochondrial respiration and increased TCA cycle and OXPHOS-related genes were observed in the Curcumae Radix group. Conclusions: In neurodegenerative diseases involving mitochondrial dysfunction, Curcumae Radix may act as a metabolic modulator of brain health to treat and prevent these diseases.

scholarly journals Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner

2020 ◽  
Vol 13 (10) ◽  
pp. dmm047134
Author(s):  
Leonie Drews ◽  
Marcel Zimmermann ◽  
Philipp Westhoff ◽  
Dominik Brilhaus ◽  
Rebecca E. Poss ◽  
...  
Keyword(s):  
Amino Acids ◽  
Energy Metabolism ◽  
Glutamate Dehydrogenase ◽  
Mitochondrial Respiration ◽  
Tca Cycle ◽  
Dependent Manner ◽  
Independent Manner ◽  
The Tca Cycle ◽  
Branched Chain ◽  
Tca Cycle Intermediates

ABSTRACTAstrocyte dysfunction is a primary factor in hepatic encephalopathy (HE) impairing neuronal activity under hyperammonemia. In particular, the early events causing ammonia-induced toxicity to astrocytes are not well understood. Using established cellular HE models, we show that mitochondria rapidly undergo fragmentation in a reversible manner upon hyperammonemia. Further, in our analyses, within a timescale of minutes, mitochondrial respiration and glycolysis were hampered, which occurred in a pH-independent manner. Using metabolomics, an accumulation of glucose and numerous amino acids, including branched chain amino acids, was observed. Metabolomic tracking of 15N-labeled ammonia showed rapid incorporation of 15N into glutamate and glutamate-derived amino acids. Downregulating human GLUD2 [encoding mitochondrial glutamate dehydrogenase 2 (GDH2)], inhibiting GDH2 activity by SIRT4 overexpression, and supplementing cells with glutamate or glutamine alleviated ammonia-induced inhibition of mitochondrial respiration. Metabolomic tracking of 13C-glutamine showed that hyperammonemia can inhibit anaplerosis of tricarboxylic acid (TCA) cycle intermediates. Contrary to its classical anaplerotic role, we show that, under hyperammonemia, GDH2 catalyzes the removal of ammonia by reductive amination of α-ketoglutarate, which efficiently and rapidly inhibits the TCA cycle. Overall, we propose a critical GDH2-dependent mechanism in HE models that helps to remove ammonia, but also impairs energy metabolism in mitochondria rapidly.

scholarly journals Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries

2015 ◽  
Vol 309 (9) ◽  
pp. H1490-H1500 ◽  
Author(s):  
Ibolya Rutkai ◽  
Somhrita Dutta ◽  
Prasad V. Katakam ◽  
David W. Busija
Keyword(s):  
Mitochondrial Respiration ◽  
Ex Vivo ◽  
Cerebral Arteries ◽  
Anion Channel ◽  
Basal Respiration ◽  
Male Rat ◽  
Sprague Dawley ◽  
Voltage Dependent Anion Channel ◽  
Male And Female ◽  
Atp Production

Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using Nω-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I–V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury.

scholarly journals Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Jarmon G. Lees ◽  
Timothy S. Cliff ◽  
Amanda Gammilonghi ◽  
James G. Ryall ◽  
Stephen Dalton ◽  
...  
Keyword(s):  
Cell Fate ◽  
Metabolic Flux ◽  
Tca Cycle ◽  
Antioxidant Response ◽  
Open Chromatin ◽  
Rna Seq ◽  
Atp Production ◽  
The Tca Cycle ◽  
Demethylase Activity ◽  
The Impact

Metabolism has been shown to alter cell fate in human pluripotent stem cells (hPSC). However, current understanding is almost exclusively based on work performed at 20% oxygen (air), with very few studies reporting on hPSC at physiological oxygen (5%). In this study, we integrated metabolic, transcriptomic, and epigenetic data to elucidate the impact of oxygen on hPSC. Using 13C-glucose labeling, we show that 5% oxygen increased the intracellular levels of glycolytic intermediates, glycogen, and the antioxidant response in hPSC. In contrast, 20% oxygen increased metabolite flux through the TCA cycle, activity of mitochondria, and ATP production. Acetylation of H3K9 and H3K27 was elevated at 5% oxygen while H3K27 trimethylation was decreased, conforming to a more open chromatin structure. RNA-seq analysis of 5% oxygen hPSC also indicated increases in glycolysis, lysine demethylases, and glucose-derived carbon metabolism, while increased methyltransferase and cell cycle activity was indicated at 20% oxygen. Our findings show that oxygen drives metabolite flux and specifies carbon fate in hPSC and, although the mechanism remains to be elucidated, oxygen was shown to alter methyltransferase and demethylase activity and the global epigenetic landscape.

scholarly journals Quantitative Assessment of Occipital Metabolic and Energetic Changes in Parkinson’s Patients, Using In Vivo 31P MRS-Based Metabolic Imaging at 7T

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 145
Author(s):  
Xiao-Hong Zhu ◽  
Byeong-Yeul Lee ◽  
Paul Tuite ◽  
Lisa Coles ◽  
Abhishek G. Sathe ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Intracellular Ph ◽  
Imaging Techniques ◽  
Neurological Deficits ◽  
Response To Treatment ◽  
Metabolic Imaging ◽  
Atp Production ◽  
31P Mrs

Abnormal energy metabolism associated with mitochondrial dysfunction is thought to be a major contributor to the progression of neurodegenerative diseases such as Parkinson’s disease (PD). Recent advancements in the field of magnetic resonance (MR) based metabolic imaging provide state-of-the-art technologies for non-invasively probing cerebral energy metabolism under various brain conditions. In this proof-of-principle clinical study, we employed quantitative 31P MR spectroscopy (MRS) imaging techniques to determine a constellation of metabolic and bioenergetic parameters, including cerebral adenosine triphosphate (ATP) and other phosphorous metabolite concentrations, intracellular pH and nicotinamide adenine dinucleotide (NAD) redox ratio, and ATP production rates in the occipital lobe of cognitive-normal PD patients, and then we compared them with age-sex matched healthy controls. Small but statistically significant differences in intracellular pH, NAD and ATP contents and ATPase enzyme activity between the two groups were detected, suggesting that subtle defects in energy metabolism and mitochondrial function are quantifiable before regional neurological deficits or pathogenesis begin to occur in these patients. Pilot data aiming to evaluate the bioenergetic effect of mitochondrial-protective bile acid, ursodeoxycholic acid (UDCA) were also obtained. These results collectively demonstrated that in vivo 31P MRS-based neuroimaging can non-invasively and quantitatively assess key metabolic-energetic metrics in the human brain. This provides an exciting opportunity to better understand neurodegenerative diseases, their progression and response to treatment.

scholarly journals Energy Metabolism Decline in the Aging Brain; Pathogenesis of Neurodegenerative Disorders

2020 ◽  
Author(s):  
Janusz Błaszczyk
Keyword(s):  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Krebs Cycle ◽  
Brain Structures ◽  
The Elderly ◽  
Review Article ◽  
Aging Brain ◽  
Salvage Pathway ◽  
Atp Production ◽  
The Brain

A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.

scholarly journals Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jared S. Mackenzie ◽  
Dirk A. Lamprecht ◽  
Rukaya Asmal ◽  
John H. Adamson ◽  
Khushboo Borah ◽  
...  
Keyword(s):  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Metabolic Flux ◽  
Tca Cycle ◽  
Central Carbon Metabolism ◽  
Atp Production ◽  
Isotopomer Analysis ◽  
Metabolic Mechanism ◽  
Substantial Interest ◽  
Insight Into

AbstractThe approval of bedaquiline (BDQ) for the treatment of tuberculosis has generated substantial interest in inhibiting energy metabolism as a therapeutic paradigm. However, it is not known precisely how BDQ triggers cell death in Mycobacterium tuberculosis (Mtb). Using 13C isotopomer analysis, we show that BDQ-treated Mtb redirects central carbon metabolism to induce a metabolically vulnerable state susceptible to genetic disruption of glycolysis and gluconeogenesis. Metabolic flux profiles indicate that BDQ-treated Mtb is dependent on glycolysis for ATP production, operates a bifurcated TCA cycle by increasing flux through the glyoxylate shunt, and requires enzymes of the anaplerotic node and methylcitrate cycle. Targeting oxidative phosphorylation (OXPHOS) with BDQ and simultaneously inhibiting substrate level phosphorylation via genetic disruption of glycolysis leads to rapid sterilization. Our findings provide insight into the metabolic mechanism of BDQ-induced cell death and establish a paradigm for the development of combination therapies that target OXPHOS and glycolysis.

scholarly journals Ammonia inhibits energy metabolism in astrocytes in a rapid and GDH2-dependent manner

2019 ◽  
Author(s):  
Leonie Drews ◽  
Marcel Zimmermann ◽  
Rebecca E. Poss ◽  
Dominik Brilhaus ◽  
Laura Bergmann ◽  
...  
Keyword(s):  
Amino Acids ◽  
Energy Metabolism ◽  
Mitochondrial Respiration ◽  
Tca Cycle ◽  
Ammonia Removal ◽  
Dependent Manner ◽  
Independent Manner ◽  
The Tca Cycle ◽  
Branched Chain ◽  
Dependent Mechanism

AbstractIn hepatic encephalopathy (HE) astrocyte dysfunction is a primary factor impairing neuronal activity under hyperammonemia. We show that mitochondria in cellular HE models undergo rapid fragmentation under hyperammonemia in a reversible manner. Mitochondrial respiration and glycolysis were instantaneously hampered in a pH-independent manner. A metabolomics approach revealed a subsequent accumulation of numerous amino acids, including branched chain amino acids, and glucose. N15labeling of ammonia shows rapid incorporation of ammonia-derived nitrogen into glutamate and glutamate-derived amino acids. Downregulating humanGLUD2, encoding mitochondrial glutamate dehydrogenase 2 (GDH2), inhibiting GDH2 activity by SIRT4 overexpression, and supplementing cells with glutamate or glutamine alleviated ammonia-induced inhibition of mitochondrial respiration. Thus, under hyperammonemic conditions, GDH2 catalyzes the removal of ammonia by reductive amination of α-ketoglutarate but at the same time inhibits the TCA-cycle by depleting α-ketoglutarate. Overall, we propose a mitochondria-dependent mechanism contributing to the early steps in the pathogenesis of HE where the interplay between energy metabolism and ammonia removal plays a pivotal role.

scholarly journals Metabolomics Analysis ofCistus monspeliensisLeaf Extract on Energy Metabolism Activation in Human Intestinal Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yoichi Shimoda ◽  
Junkyu Han ◽  
Kiyokazu Kawada ◽  
Abderrazak Smaoui ◽  
Hiroko Isoda
Keyword(s):  
Energy Metabolism ◽  
Tca Cycle ◽  
Point Of View ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Important Process ◽  
Antioxidant Ability ◽  
Atp Production ◽  
Human Intestinal Epithelial Cells ◽  
Human Intestinal Cells

Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells.Cistus monspeliensisis widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study,C. monspeliensiswas investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells.C. monspeliensisextract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced byC. monspeliensistreatment. These results suggest thatC. monspeliensisextract has an ability to enhance the energy metabolism in human intestinal cells.

Energy metabolism of preimplantation mammalian blastocysts

1983 ◽  
Vol 245 (1) ◽  
pp. C40-C45 ◽  
Author(s):  
D. J. Benos ◽  
R. S. Balaban
Keyword(s):  
Energy Consumption ◽  
Energy Metabolism ◽  
Total Energy ◽  
Mitochondrial Respiration ◽  
Energy Production ◽  
Na Transport ◽  
Total Energy Consumption ◽  
Atp Production ◽  
Transepithelial Na Transport ◽  
The Relationship

We have measured the relative contributions of glycolytic and oxidative energy production pathways of metabolism in rabbit and mouse preimplantation blastocysts. We have further studied the relationship between these pathways and active transepithelial Na+ transport. Our results show that over 85% of all ATP production arises from mitochondrial respiration. By using amphotericin B to increase the Na+ permeability of the apical (or uterine-facing) membrane of the blastocyst, we have determined that the ratio of ouabain-sensitive Na+ influx to ATP consumption is 3. Based on the measurements of ouabain-sensitive Na+ influx across blastocysts incubated in glucose-containing medium, only 6% of the total energy consumption of the embryo is used for active transepithelial Na+ transport.

scholarly journals The Role of Dietary Saturated Fat in Associations between Exposure to Ambient Fine Particulate Matter and Mitochondrial Respiratory Functions in Circulating Platelets

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 523-523
Author(s):  
Wan Shen ◽  
Hao Chen ◽  
James Samet ◽  
Haiyan Tong
Keyword(s):  
Oxygen Consumption ◽  
Mitochondrial Respiration ◽  
Saturated Fatty Acids ◽  
Fine Particulate Matter ◽  
Saturated Fat ◽  
Basal Respiration ◽  
Mitochondrial Oxygen Consumption ◽  
Atp Production ◽  
Consumption Rates ◽  
Mitochondrial Respiratory

Abstract Objectives Exposure to ambient fine particulate matter (PM2.5) is associated with platelet activation and increased mitochondrial respiration. The impact of dietary saturated fat on the circulating platelets is not understood. This project aimed to determine whether dietary saturated fatty acids moderate mitochondrial respiratory function in circulating platelets after short-term exposure to PM2.5. Methods Platelets were isolated from 22 healthy male volunteers (mean age ± SD, 37 ± 8.2) in a panel study and measured for mitochondrial oxygen consumption rates using an extracellular flux analyzer. Intakes of saturated fat were determined from 24 hr dietary recalls the day before the assay. Daily ambient PM2.5 concentrations during the study period were obtained from ambient air quality monitoring stations. Data were fitted with a moderation model, where the level of ambient PM2.5 was the independent variable, saturated fat intake was the moderator, and mitochondrial respiratory functions in circulating platelets were the dependent variables. Results After controlling for age, dietary consumption of saturated fat moderated the mitochondrial oxygen consumption rates of non-mitochondrial respiration, basal respiration, maximum respiration, ATP production, and spare respiratory capacity after exposure to ambient PM2.5 with 2 days lag. Specifically, the negative associations between the above mentioned mitochondrial respiratory measurements and PM2.5 levels reached statistical significance (95% Confident Intervals did not include 0) in subjects with a high intake of total saturated fat. Further, results for individual saturated fatty acid showed similar patterns, specifically that negative association between mitochondrial oxygen consumption rates of non-mitochondrial respiration, basal respiration and ATP production and levels of exposed PM2.5 was moderated by intakes of short-chain (C4:0), medium-chain (C6:0, C8:0, C10:0, C12:0), long-chain (C14:0, C16:0) saturated fatty acids. Conclusions Taken together, these preliminary findings suggest that consumption of saturated fat moderates platelet mitochondrial respiration after exposure to PM2.5.  THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY. Funding Sources This project was supported by the U.S. EPA Intramural Research Program.

Sign in / Sign up

Export Citation Format

Share Document