Anaerobic Glycolysis in Normal Human Erythrocytes Incubated in Vitro with Sodium Salicylate

1975 ◽  
Vol 49 (5) ◽  
pp. 375-384
Author(s):  
N. Worathumrong ◽  
A. J. Grimes

1. Some effects of sodium salicylate upon anaerobic glycolysis have been studied in normal human erythrocytes incubated for up to 6 h at 37°C in autologous sera. 2. Both glucose consumption and lactate production were stimulated by concentrations of salicylate up to 60 mmol/l but at the highest concentration used (90 mmol/l) an initial stimulus was followed by inhibition of glycolysis. 3. Losses occurred of adenosine 5′-triphosphate (ATP), adenosine 5′-diphosphate (ADP) and adenosine 5′-phosphate (AMP) at higher concentrations of salicylate and there was a concomitant increase of inorganic phosphate. 4. Other phosphate esters underwent concentration changes at higher concentrations of salicylate that reflected inadequate concentrations of ATP for glycolysis. 5. The rates of sodium efflux from, and potassium influx into, erythrocytes were unaffected by the presence of salicylate at concentrations sufficient to stimulate glycolysis.

1966 ◽  
Vol 51 (2) ◽  
pp. 193-202
Author(s):  
J. A. Antonioli ◽  
A. Vannotti

ABSTRACT 1. The metabolism of suspensions of circulating leucocytes has been studied after intramuscular injection of a dose of 50 mg/kg of a corticosteroid (cortisone acetate). The suspensions were incubated under aerobic conditions in the presence of a glucose concentration of 5.6 mm. Glucose consumption, lactate production, and variations in intracellular glycogen concentration were measured. After the administration of the corticosteroid, the anabolic processes of granulocyte metabolism were reversibly stimulated. Glucose consumption and lactate production increased 12 hours after the injection, but tended to normalize after 24 hours. The glycogen content of the granulocytes was enhanced, and glycogen synthesis during the course of the incubation was greatly stimulated. The action of the administered corticosteroid is more prolonged in females than in males. The injection of the corticosteroid caused metabolic modifications which resemble in their modulations and in their chronological development those found in circulating granulocytes of guinea-pigs suffering from sterile peritonitis. These results suggest, therefore, that, in the case of acute inflammation, the glucocorticosteroids may play an important role in the regulation of the metabolism of the blood leucocytes.


1987 ◽  
Author(s):  
R N I Pietersz ◽  
D de Korte ◽  
D Roos ◽  
H W Reesink

Leukocyte poor platelet concentrates (PC), containing less than 10 leukocytes, prepared from buffycoats can be stored in normal PVC bags for 7 days at 22°C without deterioration of the pH. We assumed that a low number of leukocytes present in the PC, is a critical factor to maintain the pH. To test this hypothesis increasing amounts of leukocytes were added to four groups of three PC with comparable plasma volumes (mean 58.6 ± 0.8 (SD) ml) and platelet concentrations (1.01 ± 0.04×109 /ml). Group I had a leukocyte concentration of 0.14±0.048×106 /ml, group II 1.96±0.09×106 /ml, group III 5.53±0.98×106 /ml, and group IV 13.0±0.93×106 /ml. The PC were stored in normal PVC bags for 7 days at 22°C. Measurements in vitro were performed at day 0, 2, 5 and 7.The initial mean pH value was 7.12±0.02 (SD) for all PC and dropped to 6.89, 6.85, 6.77 and 6.61 for group I to IV respectively, at day 7. A significant correlation (Spearman rank test) between low pH values and high leukocytes was found. The same significant positive correlation was observed between high leukocyte concentrations and high glucose consumption and high lactate production and LDH release during storage.These results show that the amount of leukocytes in PC has a significant contribution to the detrimental effect on pH during platelet storage. It is therefore important to prepare PC with a leukocyte count lower than 10 . Moreover the risk of alloimmunisation against HLA antigens will be diminished.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Weixing Dai ◽  
Xianke Meng ◽  
Shaobo Mo ◽  
Wenqiang Xiang ◽  
Ye Xu ◽  
...  

Abstract Background Low expression of FOXE1, a member of Forkhead box (FOX) transcription factor family that plays vital roles in cancers, contributes to poor prognosis of colorectal cancer (CRC) patients. However, the underlying mechanism remains unclear. Materials and methods The effects of FOXE1 on the growth of colon cancer cells and the expression of glycolytic enzymes were investigated in vitro and in vivo. Molecular biological experiments were used to reveal the underlying mechanisms of altered aerobic glycolysis. CRC tissue specimens were used to determine the clinical association of ectopic metabolism caused by dysregulated FOXE1. Results FOXE1 is highly expressed in normal colon tissues compared with cancer tissues and low expression of FOXE1 is significantly associated with poor prognosis of CRC patients. Silencing FOXE1 in CRC cell lines dramatically enhanced cell proliferation and colony formation and promoted glucose consumption and lactate production, while enforced expression of FOXE1 manifested the opposite effects. Mechanistically, FOXE1 bound directly to the promoter region of HK2 and negatively regulated its transcription. Furthermore, the expression of FOXE1 in CRC tissues was negatively correlated with that of HK2. Conclusion FOXE1 functions as a critical tumor suppressor in regulating tumor growth and glycolysis via suppressing HK2 in CRC.


Reproduction ◽  
2005 ◽  
Vol 130 (4) ◽  
pp. 475-483 ◽  
Author(s):  
Kimberly A Preis ◽  
George Seidel ◽  
David K Gardner

In vitro maturation of oocytes has enormous potential in assisted reproductive technology, but its use has been limited due to insufficient knowledge of oocyte physiology during this dynamic period and lack of an adequate maturation system. The aim of this study was to characterize the metabolic profiles of three groups of oocytes throughout maturation: cumulus–oocyte complexes (COCs), denuded oocytes, and denuded oocytes co-cultured with cumulus cells. Mouse oocytes were collected from 28-day-old unstimulated females and matured in a defined medium. Oocytes were matured individually and transferred into fresh 0.5 μl drops of medium at 4 h intervals until 16 h. Ultramicrofluorimetry was used to quantitate carbohydrate consumption from and metabolite release into the medium. Glucose consumption and lactate production of COCs increased (P < 0.001) over the maturation interval (0–16 h). Glucose consumption by COCs that subsequently fertilized was higher between 8–12 h of maturation than by COCs that did not fertilize (38 versus 29 pmol/COC per h, respectively; P < 0.01). Lactate production by COCs that subsequently fertilized was higher between 8–16 h of maturation, than by oocytes that did not fertilize (8–12 h, 66 versus 46 pmol/COC per h, P < 0.01; 12–16 h, 56 versus 40 pmol/COC per h, respectively; P < 0.05). These data indicate that the final hours of maturation may hold a unique marker of oocyte competence, as during this time fertilizable COCs take up more glucose and produce more lactate than those not subsequently fertilized.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15123-e15123
Author(s):  
Dawei Li ◽  
Qingguo Li ◽  
Sanjun Cai ◽  
Keping Xie

e15123 Background: Aberrant expression of Forkhead Box transcription factors plays vital roles in the oncogenesis and metastasis of many types of cancer. The purpose of this study is to elucidate the function of Forkhead Box C1(FOXC1) in colorectal cancer (CRC)malignancy maintenance. Methods: FOXC1 expression in CRC specimens was analyzed in the TCGA database and validated by immunohistochemistry using a tissue microarray (TMA). The effect of FOXC1 expression on cancer proliferation and glycolysis was assessed in cells by altering the expression of FOXC1 in vitro and in vivo. Mechanistic investigation was carried out by using cell and molecular biology approaches. Results: FOXC1 was found to be overexpressed in CRC specimens compared with that in the adjacent benign tissues. Univariate survival analyses of the TCGA and validated cohorts showed that high expression of FOXC1 was significantly correlated with shortened patient survival ( P< 0.05). Attenuation of FOXC1 expression inhibited proliferation, clone formation and decreased glucose consumption and lactate production. By contrast, overexpression of FOXC1 had the opposite effect. Furthermore, increased FOXC1 expression downregulated the expression of a key glycolytic enzyme,fructose-1, 6-Bisphosphatase 1 (FBP1). Mechanistically, FOXC1 bound directly to the promoter regions of the FBP1 gene and negatively regulated its transcriptional activity. Aberrant FBP1 expression contributes to CRC tumorigenicity, and decreased FBP1 coupled with increased FOXC1 provided better prognostic information than FOXC1 did alone. Conclusions: The FOXC1/FBP1 axis induces cell proliferation, reprograms the metabolic process in CRC and provides potential prognostic predictors and therapeutic targets for patients with CRC.


Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1814
Author(s):  
Sonam Kumari ◽  
Mohammed Sikander ◽  
Shabnam Malik ◽  
Manish K. Tripathi ◽  
Bilal B. Hafeez ◽  
...  

Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanisms that are responsible for high glucose metabolism and identify natural/synthetic agents that can repress glucose metabolic machinery in pancreatic cancer cells, to improve the therapeutic outcomes/management of pancreatic cancer patients. We have identified a glycoside, steviol that effectively represses glucose consumption in pancreatic cancer cells via the inhibition of the translation initiation machinery of the molecular components. Herein, we report that steviol effectively inhibits the glucose uptake and lactate production in pancreatic cancer cells (AsPC1 and HPAF-II). The growth, colonization, and invasion characteristics of pancreatic cancer cells were also determined by in vitro functional assay. Steviol treatment also inhibited the tumorigenic and metastatic potential of human pancreatic cancer cells by inducing apoptosis and cell cycle arrest in the G1/M phase. The metabolic shift by steviol was mediated through the repression of the phosphorylation of mTOR and translation initiation proteins (4E-BP1, eIF4e, eIF4B, and eIF4G). Overall, the results of this study suggest that steviol can effectively suppress the glucose metabolism and translation initiation in pancreatic cancer cells to mitigate their aggressiveness. This study might help in the design of newer combination therapeutic strategies for pancreatic cancer treatment.


Toxins ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 464 ◽  
Author(s):  
Constanze Nossol ◽  
Peter Landgraf ◽  
Stefan Kahlert ◽  
Michael Oster ◽  
Berend Isermann ◽  
...  

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.


Reproduction ◽  
2007 ◽  
Vol 134 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Sarah E Harris ◽  
Iris Adriaens ◽  
Henry J Leese ◽  
Roger G Gosden ◽  
Helen M Picton

Metabolic markers are potentially valuable for assessment of follicle development in vitro. Carbohydrate metabolism of murine preantral follicles grown to maturityover 13 days in vitro has been measured, and metabolism of resulting oocyte–cumulus complexes (OCCs) and denuded oocytes has been compared with in vivo ovulated control counterparts. Spent follicle culture media were analysed for glucose, lactate and pyruvate concentrations. During follicle in vitro growth, glycolysis accounted for a rise from ∼24 to 60% of all glucose consumed. Ovulation induction caused a significant increase in glucose uptake and lactate production by in vitro-grown follicles to 71.7±1.2 and 96.6±4.8 nmoles/day respectively. OCCs grown in vitro had significantly higher rates of glucose consumption and lactate and pyruvate production (110.1± 3.5, 191.8± 8.9 and 31.7± 1.7 pmoles/h respectively) than in vivo ovulated controls (67.4± 8.1, 113.9± 17.1 and 20.2± 4.0 pmoles/h respectively), but a reduced capacity for pyruvate consumption (1.13± 0.06 vs 1.49± 0.06 pmoles/h by in vivo ovulated oocytes). Metabolism of OCCs was affected by the quality of the original follicle. In vitro-grown oocytes had a reduced cytoplasmic volume when compared with controls (168.3± 2.0 vs 199.0± 3.2 proportionately respectively) but a similar rate of metabolism per unit volume. Meiotic status influenced metabolism of both OCCs and denuded oocytes. In conclusion, glucose consumption and lactate production by cultured follicles increased in tandem with developmental progression and were stimulated prior to ovulation. Additionally, the metabolic profiles of in vitro produced OCCs and the oocytes within them are affected by long-term exposure to the culture environment.


2016 ◽  
Vol 28 (12) ◽  
pp. 1926 ◽  
Author(s):  
Hilde Nelis ◽  
Bartosz Wojciechowicz ◽  
Anita Franczak ◽  
Bart Leemans ◽  
Katharina D'Herde ◽  
...  

The oviduct undergoes dramatic functional and morphological changes throughout the oestrous cycle of the mare. To unravel the effects of steroids on the morphology, functionality and gene expression of the equine oviduct, an in vitro oviduct explant culture system was stimulated with physiological concentrations of progesterone and 17β-oestradiol. Four conditions were compared: unsupplemented preovulatory explants, preovulatory explants that were stimulated with postovulatory hormone concentrations, unsupplemented postovulatory explants and postovulatory explants that were stimulated with preovulatory hormone concentrations. The modulating effects of both steroids on oviduct explants were investigated and the following parameters examined: (1) ciliary activity, (2) glucose consumption and lactate production pattern, (3) ultrastructure, (4) mRNA expression of embryotrophic genes, (5) steroidogenic capacities of oviductal explants and (6) progesterone receptor expression. The present paper shows that the equine oviduct is an organ with potential steroidogenic capacities, which is highly responsive to local changes in progesterone and 17β-oestradiol concentrations at the level of morphology, functionality and gene expression of the oviduct. These data provide a basis to study the importance of endocrine and paracrine signalling during early embryonic development in the horse.


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