An Imaging Approach to Assess the Impact of Systemic Hypoxia on Pulmonary Lactate Production: A Hyperpolarized Carbon-13 Study

The impact of glycolysis on rat spermatid energy metabolism is made apparent by the simultaneous occurrence of the following three events upon glucose addition to the extracellular medium of a rat spermatid cell suspension: decrease in ATP content, exit of acid equivalents, and increased lactate production and efflux. In this work, we have studied the interrelations between these three phenomena. By measuring ATP content, net acid transport, lactate exit, oxygen consumption, intracellular pH, CO2 production, and glycolytic intermediates in the presence of glucose and glucose analogues, we conclude that 1) lactate production, decrease in ATP content, and acid equivalent exit are dependent on the metabolism of glucose up to different stages in glycolysis. 2) The decrease in ATP content is not directly related to the exit of acid equivalents from rat spermatids. 3) Glucose metabolism is a net ATP-consuming process at high intracellular ATP content but is a net ATP-producing process at low intracellular ATP concentration in rat spermatids. 4) Acid equivalent production arises from the metabolism of glucose beyond glyceraldehyde 3-phosphate dehydrogenase. 5) Lactic acid diffusion and/or lactate transport and CO2 production and exit could account for the glucose-dependent acid equivalent efflux in rat spermatids.

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Mitochondrial genome and its regulator TFAM modulates head and neck tumourigenesis through intracellular metabolic reprogramming and activation of oncogenic effectors

Cell Death and Disease ◽

10.1038/s41419-021-04255-w ◽

2021 ◽

Vol 12 (11) ◽

Author(s):

Yi-Ta Hsieh ◽

Hsi-Feng Tu ◽

Muh-Hwa Yang ◽

Yi-Fen Chen ◽

Xiang-Yun Lan ◽

...

Keyword(s):

Head And Neck ◽

Tongue Cancer ◽

Aerobic Glycolysis ◽

Lactate Production ◽

Cellular Level ◽

Metabolic Reprogramming ◽

Transport Chain ◽

Genetically Manipulated ◽

The Impact

AbstractMitochondrial transcriptional factor A (TFAM) acts as a key regulatory to control mitochondrial DNA (mtDNA); the impact of TFAM and mtDNA in modulating carcinogenesis is controversial. Current study aims to define TFAM mediated regulations in head and neck cancer (HNC). Multifaceted analyses in HNC cells genetically manipulated for TFAM were performed. Clinical associations of TFAM and mtDNA encoded Electron Transport Chain (ETC) genes in regulating HNC tumourigenesis were also examined in HNC specimens. At cellular level, TFAM silencing led to an enhanced cell growth, motility and chemoresistance whereas enforced TFAM expression significantly reversed these phenotypic changes. These TFAM mediated cellular changes resulted from (1) metabolic reprogramming by directing metabolism towards aerobic glycolysis, based on the detection of less respiratory capacity in accompany with greater lactate production; and/or (2) enhanced ERK1/2-Akt-mTORC-S6 signalling activity in response to TFAM induced mtDNA perturbance. Clinical impacts of TFAM and mtDNA were further defined in carcinogen-induced mouse tongue cancer and clinical human HNC tissues; as the results showed that TFAM and mtDNA expression were significantly dropped in tumour compared with their normal counterparts and negatively correlated with disease progression. Collectively, our data uncovered a tumour-suppressing role of TFAM and mtDNA in determining HNC oncogenicity and potentially paved the way for development of TFAM/mtDNA based scheme for HNC diagnosis.

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Long-term HIF-1α transcriptional activation is essential for heat-acclimation-mediated cross tolerance: mitochondrial target genes

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00461.2016 ◽

2017 ◽

Vol 312 (5) ◽

pp. R753-R762 ◽

Cited By ~ 6

Author(s):

Rivka Alexander-Shani ◽

Ahmad Mreisat ◽

Elia Smeir ◽

Gary Gerstenblith ◽

Michael D. Stern ◽

...

Keyword(s):

Transcriptional Activation ◽

Target Genes ◽

Ischemia Reperfusion ◽

Mitochondrial Gene ◽

Lactate Production ◽

Heat Acclimation ◽

Cross Tolerance ◽

Metabolic Switch ◽

Atp Production ◽

The Impact

An important adaptive feature of heat acclimation (HA) is the induction of cross tolerance against novel stressors (HACT) Reprogramming of gene expression leading to enhanced innate cytoprotective features by attenuating damage and/or enhancing the response of “help” signals plays a pivotal role. Hypoxia-inducible factor-1α (HIF-1α), constitutively upregulated by HA (1 mo, 34°C), is a crucial transcription factor in this program, although its specific role is as yet unknown. By using a rat HA model, we studied the impact of disrupting HIF-1α transcriptional activation [HIF-1α:HIF-1β dimerization blockade by intraperitoneal acriflavine (4 mg/kg)] on its mitochondrial gene targets [phosphoinositide-dependent kinase-1 (PDK1), LON, and cyclooxygenase 4 (COX4) isoforms] in the HA rat heart. Physiological measures of cardiac HACT were infarct size after ischemia-reperfusion and time to rigor contracture during hypoxia in cardiomyocytes. We show that HACT requires transcriptional activation of HIF-1α throughout the course of HA and that this activation is accompanied by two metabolic switches: 1) profound upregulation of PDK1, which reduces pyruvate entry into the mitochondria, consequently increasing glycolytic lactate production; 2) remodeling of the COX4 isoform ratio, inducing hypoxic-tolerant COX4.2 dominance, and optimizing electron transfer and possibly ATP production during the ischemic and hypoxic insults. LON and COX4.2 transcript upregulation accompanied this shift. Loss of HACT despite elevated expression of the cytoprotective protein heat shock protein-72 concomitantly with disrupted HIF-1α dimerization suggests that HIF-1α is essential for HACT. The role of a PDK1 metabolic switch is well known in hypoxia acclimation but not in the HA model and its ischemic setting. Remodeling of COX4 isoforms by environmental acclimation is a novel finding.

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Preserved placental oxygenation and development during severe systemic hypoxia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00237.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. R844-R851 ◽

Cited By ~ 24

Author(s):

Leonhard Schäffer ◽

Johannes Vogel ◽

Christian Breymann ◽

Max Gassmann ◽

Hugo H. Marti

Keyword(s):

Hypoxia Inducible Factor ◽

Central Area ◽

Placental Tissue ◽

Tissue Hypoxia ◽

Placental Development ◽

Systemic Hypoxia ◽

Pregnant Mice ◽

Endothelial Nitric Oxide ◽

The Impact

Local tissue oxygenation profoundly influences placental development. To elucidate the impact of hypoxia on cellular and molecular adaptation in vivo, pregnant mice at embryonic days 7.5–11.5 were exposed to reduced environmental oxygen (6–7% O2) for various periods of time. Hypoxia-inducible factor (HIF)-1α mRNA was highly expressed in the placenta, whereas HIF-2α was predominantly found in the decidua, indicating that HIF-1 is a relevant oxygen-dependent factor involved in placental development. During severe hypoxia, HIF-1α protein was strongly induced in the periphery but, however, not in the labyrinth layer of the placenta. Accordingly, no indication for tissue hypoxia in this central area was detected with 2-(2-nitro-1 H-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl)acetamide staining and VEGF expression as hypoxic markers. The absence of significant tissue hypoxia was reflected by preserved placental architecture and trophoblast differentiation. In the search for mechanisms preventing local hypoxia, we found upregulation of endothelial nitric oxide synthase (NOS) expression in the labyrinth layer. Inhibition of NOS activity by Nω-nitro-l-arginine methyl ester application resulted in ubiquitous placental tissue hypoxia. Our results show that placental oxygenation is preserved even during severe systemic hypoxia and imply that NOS-mediated mechanisms are involved to protect the placenta from maternal hypoxia.

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New azimuthal binning for improved delineation of faults and fractures

Geophysics ◽

10.1190/1.2813136 ◽

2008 ◽

Vol 73 (1) ◽

pp. S7-S15 ◽

Cited By ~ 17

Author(s):

Gabriel Perez ◽

Kurt J. Marfurt

Keyword(s):

Azimuthal Velocity ◽

Image Point ◽

Fort Worth ◽

Fracture Detection ◽

Prestack Migration ◽

Fort Worth Basin ◽

Strike Direction ◽

Scattered Energy ◽

Imaging Approach ◽

The Impact

We suggest and test a new way to define azimuth binning in Kirchhoff prestack migration. With this new definition, we sort seismic data by the azimuth of the average travel path traversed from the source to the subsurface image point and back to the receiver, rather than the azimuth between source and receiver on the surface of the earth. This approach avoids mixing the typically weaker side-scattered energy with the stronger in-plane reflections, thereby providing greater leverage in identifying image contributions from out-of-the-plane steeply dipping reflectors, fractures and faults. We examine the impact of this new imaging approach combined with analysis of seismic attributes that have proved useful for fracture detection, on data from the Fort Worth Basin, Texas, United States. We find that the image of features such as reflectors and discontinuities focus into azimuths perpendicular to the strike of each feature. The discrimination achieved in the azimuthal domain allows for an increased resolution in analysis of geologic features according to their strike direction. It should also result in improved residual azimuthal velocity analysis.

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The Study of Holey Cavity in the Application of Thermoacoustics Imaging

Volume 11: Acoustics, Vibration, and Phononics ◽

10.1115/imece2018-87757 ◽

2018 ◽

Author(s):

Chang Liu ◽

Ashkan Ghanbarzadeh-Dagheyan ◽

Juan Heredia-Juesas ◽

Ali Molaei ◽

Jose Angel Martinez-Lorenzo

Keyword(s):

High Spatial Resolution ◽

Subsurface Imaging ◽

Alternating Direction ◽

Imaging Results ◽

Cavity Structure ◽

Imaging Approach ◽

Minimum Number ◽

Imaging Theory ◽

Imaging Performance ◽

The Impact

Microwave-induced Thermoacoustics (TA) sensing has the potential to be a breakthrough in subsurface imaging applications. This is because it combines the advantages of high contrast of microwave imaging and high resolution of ultrasound imaging. However, state-of-the-art TA hardware requires that the receiving transducer is scanned in a linear or rotational fashion in order to be able to collect enough orthogonal data needed to produce a TA image possessing high-spatial resolution both in range and cross-range. This process is slow, increases the detection time, and adds an extra complexity to the system. In order to address these problems, a Compressive Sensing (CS) methodology is presented in this paper as a mechanism to reduce the minimum number of data samples required to reconstruct a sparse signal. Furthermore, in order to reduce the mutual information shared by different measurements, a holey cavity structure is proposed to be used to perform 4D coding. In this work, the TA imaging theory is introduced; and the impact that the holey cavity parameters have in the imaging performance is studied. The imaging results in this work are carried out using a distributed Alternating Direction Method of Multipliers (ADMM) algorithm, capable of using norm-1 and norm-2 regularizers; and they reveal the effectiveness of the proposed holey-cavity and CS TA imaging approach.

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Deoxynivalenol Affects Cell Metabolism and Increases Protein Biosynthesis in Intestinal Porcine Epithelial Cells (IPEC-J2): DON Increases Protein Biosynthesis

Toxins ◽

10.3390/toxins10110464 ◽

2018 ◽

Vol 10 (11) ◽

pp. 464 ◽

Cited By ~ 4

Author(s):

Constanze Nossol ◽

Peter Landgraf ◽

Stefan Kahlert ◽

Michael Oster ◽

Berend Isermann ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

De Novo ◽

Protein Biosynthesis ◽

Lactate Production ◽

Glucose Consumption ◽

Tca Cycle ◽

Economic Losses ◽

Anaerobic Glycolysis ◽

Low Glucose ◽

The Impact

Deoxynivalenol (DON) is a toxin found in cereals as well as in processed products such as pasta, and causes substantial economic losses for stock breeding as it induces vomiting, reduced feeding, and reduced growth rates in piglets. Oxidative phosphorylation, TCA-cycle, transcription, and translation have been hypothesized to be leading pathways that are affected by DON. We used an application of high and low glucose to examine oxidative phosphorylation and anaerobic glycolysis. A change in the metabolic status of IPEC-J2 was observed and confirmed by microarray data. Measurements of oxygen consumption resulted in a significant reduction, if DON attacks from the basolateral. Furthermore, we found a dose-dependent effect with a significant reduction at 2000 ng/mL. In addition, SLC7A11 and PHB, the genes with the highest regulation in our microarray analyses under low glucose supply, were investigated and showed a variable regulation on protein level. Lactate production and glucose consumption was investigated to examine the impact of DON on anaerobic glycolysis and we observed a significant increase in 2000 blhigh and a decrease in 2000 aphigh. Interestingly, both groups as well as 200 blhigh showed a significant higher de novo protein synthesis when compared to the control. These results indicate the direct or indirect impact of DON on metabolic pathways in IPEC-J2.

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The transcriptomic response of a wine strain of Lachancea thermotolerans to oxygen deprivation

FEMS Yeast Research ◽

10.1093/femsyr/foaa054 ◽

2020 ◽

Vol 20 (7) ◽

Author(s):

Kirti Shekhawat ◽

Florian F Bauer ◽

Mathabatha E Setati

Keyword(s):

Metabolic Flux ◽

Anaerobic Fermentation ◽

Lactate Production ◽

Starter Cultures ◽

Wine Fermentation ◽

Limiting Factor ◽

Transcriptomic Response ◽

Fermentation Conditions ◽

The Impact ◽

Lachancea Thermotolerans

ABSTRACT The yeast Lachancea thermotolerans is of significant biotechnological interest, and selected strains of this species have become commonly used starter cultures in wine fermentation. However, the impact of this species on wine is frequently limited by the rapid dominance of Saccharomyces cerevisiae strains which are better adapted to wine alcoholic fermentation conditions. Previous studies have shown that the major limiting factor for L. thermotolerans competitive performance in the wine ecosystem is oxygen availability, and not ethanol levels as had been previously suggested. Here we investigated the transcriptional response of L. thermotolerans to anaerobiosis in wine fermentation conditions. The data show that L. thermotolerans broadly redirects gene expression towards genes involved in central carbon metabolism, lipid metabolism, remodeling of the cell wall as well as autophagy. Furthermore, the induction of genes that are likely involved in the generation of lactate indicates a redirection of metabolic flux towards this metabolite. The data provide the first insight into the oxygen-dependent response of L. thermotolerans and suggest potential genetic targets to improve lactate production and/or anaerobic fermentation performance of this yeast.

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The Effects of Chest Wall Loading on Perceptions of Fatigue, Exercise Performance, Pulmonary Function, and Muscle Perfusion

Sports ◽

10.3390/sports8010003 ◽

2020 ◽

Vol 8 (1) ◽

pp. 3 ◽

Cited By ~ 1

Author(s):

Gaia Giuriato ◽

Anders Gundersen ◽

Sarina Verma ◽

Ethan Pelletier ◽

Brock Bakewell ◽

...

Keyword(s):

Pulmonary Function ◽

Chest Wall ◽

Power Output ◽

Perceived Exertion ◽

Lactate Production ◽

Load Carriage ◽

Rating Of Perceived Exertion ◽

Wall Loading ◽

The Impact ◽

Over Time

Background: Load carriage (LC), which directly affects the chest wall and locomotor muscles, has been suggested to alter the ventilatory and circulatory responses to exercise, leading to increased respiratory muscle work and fatigue. However, studies exploring the impact of LC on locomotion increased internal work, complicating their interpretation. To overcome this issue, we sought to determine the effect of chest wall loading with restriction (CWL + R) on cycling performance, cardiopulmonary responses, microvascular responsiveness, and perceptions of fatigue. Methods: In a randomized crossover design, 23 young healthy males (22 ± 4 years) completed a 5 km cycling time trial (TT) in loaded (CWL + R; tightened vest with 10% body weight) and unloaded conditions. After baseline pulmonary function testing (PFT; forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC), cardiopulmonary indices (HR, heart rate; O2 uptake, VO2; ventilation, VE; tidal volume, VT; and breathing frequency, Bf), rating of perceived exertion (RPE), lactate (BLa), and microvascular responses (oxy-, deoxy-, total hemoglobin; and tissue saturation; StO2) of the vastus lateralis using near infrared spectroscopy were collected during the TT; and PFT was repeated post-exercise. Results: Pre-exercise, CWL + R reduced (p < 0.05) FVC (5.6 ± 0.8 versus 5.5 ± 0.7 L), FEV1 (4.8 ± 0.7 versus 4.7 ± 0.6 L), and FEV1/FVC (0.9 ± 0.1 versus 0.8 ± 0.1). CWL + R modified power output (PO) over time (interaction, p = 0.02), although the 5 km time (461 ± 24 versus 470 ± 27 s), VT (3.0 ± 0.3 versus 2.8 ± 0.8 L), Bf, VE, HR, VO2, microvascular and perceptual (visual analog scale, or VAS, and RPE) responses were unchanged (p > 0.05). CWL + R increased (p < 0.05) the average BLa (7.6 ± 2.6 versus 8.6 ± 3 mmol/L). Conclusions: Modest CWL + R negatively affects pre-exercise pulmonary function, modifies cycling power output over time, and increases lactate production during a 5 km cycling trial, although the cardiorespiratory, microvascular, and perceptual responses were unaffected.

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Synbiotic Effect of Bifidobacterium lactis CNCM I-3446 and Bovine Milk-Derived Oligosaccharides on Infant Gut Microbiota

Nutrients ◽

10.3390/nu12082268 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2268 ◽

Cited By ~ 2

Author(s):

Benoît Marsaux ◽

Pieter Van den Abbeele ◽

Jonas Ghyselinck ◽

Guénolée Prioult ◽

Massimo Marzorati ◽

...

Keyword(s):

Gut Microbiota ◽

Bovine Milk ◽

Lactate Production ◽

Activity Level ◽

Microbial Composition ◽

Depth Study ◽

Novel Strategy ◽

Ph Decrease ◽

The Impact

Background: This study evaluated the impact of Bifidobacterium animalis ssp. lactis CNCM I-3446, Bovine Milk-derived OligoSaccharides (BMOS) and their combination on infant gut microbiota in vitro. In addition, a novel strategy consisting of preculturing B. lactis with BMOS to further enhance their potential synbiotic effects was assessed. Method: Short-term fecal batch fermentations (48 h) were used to assess the microbial composition and activity modulated by BMOS alone, B. lactis grown on BMOS or dextrose alone, or their combinations on different three-month-old infant microbiota. Results: BMOS alone significantly induced acetate and lactate production (leading to pH decrease) and stimulated bifidobacterial growth in 10 donors. A further in-depth study on two different donors proved B. lactis ability to colonize the infant microbiota, regardless of the competitiveness of the environment. BMOS further enhanced this engraftment, suggesting a strong synbiotic effect. This was also observed at the microbiota activity level, especially in a donor containing low initial levels of bifidobacteria. In this donor, preculturing B. lactis with BMOS strengthened further the early modulation of microbiota activity observed after 6 h. Conclusion: This study demonstrated the strong synbiotic effect of BMOS and B. lactis on the infant gut microbiota, and suggests a strategy to improve its effectiveness in an otherwise low-Bifidobacterium microbiota.

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