scholarly journals Direct Evidence for Glucose Consumption Acceleration by Carbonates in Cultured Cells

2019 ◽  
Author(s):  
Kenji Sorimachi
Keyword(s):  
Glucose Metabolism ◽  
Culture Medium ◽  
Direct Evidence ◽  
Cultured Cells ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Inhibitory Effects ◽  
Diabetes In Animals ◽  
High Concentrations

AbstractEstablished Py-3Y1-S2 rat fibroblast cells were used to evaluate whether NaHCO3 or Na2CO3 influences glucose metabolism in vitro, because factors that contribute to metabolic pathways are much simpler to evaluate in cultured cells than in whole animal bodies. The effects of the carbonates on glucose consumption decreased at high concentrations, >5 mg/ml for Na2CO3 and >7 mg/ml for NaHCO3, because of the increased pH of the culture medium. The effects of the carbonates on glucose consumption were additive with those of vanadium and concanavalin A. Streptozotocin, alloxan, and nicotinamide, which induce diabetes in animals, reduced glucose consumption by Py-3Y1-S2 cells, and the inhibitory effects of these reagents were abolished by both Na2CO3 and NaHCO3. Finally, the carbonates increased lactate production from glucose in the cells, followed by acceleration of lactate secretion into the culture medium. The present study clarified that NaHCO3 and Na2CO3 directly regulate glucose metabolism.

scholarly journals Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1814
Author(s):  
Sonam Kumari ◽  
Mohammed Sikander ◽  
Shabnam Malik ◽  
Manish K. Tripathi ◽  
Bilal B. Hafeez ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Translation Initiation ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Human Pancreatic Cancer ◽  
Functional Assay ◽  
Pancreatic Cancer Cells

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.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

ÉTUDE IN VITRO DU MÉTABOLISME DES HYDRATES DE CARBONE DANS LE LEUCOCYTE CIRCULANT DU COBAYE TRAITÉ À LA CORTISONE

1966 ◽  
Vol 51 (2) ◽  
pp. 193-202
Author(s):  
J. A. Antonioli ◽  
A. Vannotti
Keyword(s):  
Glucose Concentration ◽  
Intramuscular Injection ◽  
Acute Inflammation ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
List Type ◽  
Hydrates De Carbone

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.

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
Keyword(s):  
Sodium Salicylate ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Human Erythrocytes ◽  
Anaerobic Glycolysis ◽  
Initial Stimulus ◽  
Sodium Efflux ◽  
Normal Human ◽  
Concentration Changes

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.

Transcriptional control of delta-crystallin gene expression in the chicken embryo lens: demonstration by a new method for measuring mRNA metabolism

1993 ◽  
Vol 13 (6) ◽  
pp. 3282-3290
Author(s):  
X Li ◽  
D C Beebe
Keyword(s):  
Chicken Embryo ◽  
Transcriptional Control ◽  
Cultured Cells ◽  
Pcr Primers ◽  
High Refractive Index ◽  
In Vitro Transcription ◽  
Equilibrium Density ◽  
Specific Pcr ◽  
High Concentrations

Crystallins are proteins that accumulate to very high concentrations in the fiber cells of the lens of the eye. Crystallins are responsible for the transparency and high refractive index that are essential for lens function. In the chicken embryo, delta-crystallin accounts for more than 70% of the newly synthesized lens proteins. We used density labeling and gene-specific polymerase chain reaction (PCR) to determine the mechanism regulating the expression of the two very similar delta-crystallin genes. Newly synthesized RNA was separated from preexisting RNA by incubating the lenses with 15N- and 13C-labeled ribonucleosides and then separating newly synthesized, density-labeled RNA from the bulk of light RNA by equilibrium density centrifugation in NaI-KI gradients. The relative abundances of the two crystallin mRNAs in the separated fractions were then determined by PCR. This method permitted the quantitation of newly synthesized processed and unprocessed delta-crystallin mRNAs. Additional studies used intron- and gene-specific PCR primers to determine the relative expression of the two delta-crystallin genes in processed RNA and unprocessed RNA extracted from different regions of the embryonic lens. Results of these tests indicated that the differential expression of the delta-crystallin genes was regulated primarily at the level of transcription. This outcome was not expected on the basis of the results of previous studies, which used in vitro transcription and transfection methods to evaluate the relative strengths of delta-crystallin promoter and enhancer sequences. Our data suggest that the cultured cells used in these earlier studies may not have provided an accurate view of delta-crystallin regulation in the intact lens.

CONTAMINATING LEUKOCYTES INFLUENCE THE STORAGE CONDITIONS OF PLATELET CONCENTRATES

1987 ◽  
Author(s):  
R N I Pietersz ◽  
D de Korte ◽  
D Roos ◽  
H W Reesink
Keyword(s):  
Ph Value ◽  
Hla Antigens ◽  
Lactate Production ◽  
Critical Factor ◽  
Glucose Consumption ◽  
Storage Conditions ◽  
Rank Test ◽  
Platelet Concentrates ◽  
Group I

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.

scholarly journals Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Baochi Ou ◽  
Hongze Sun ◽  
Jingkun Zhao ◽  
Zhuoqing Xu ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Transcriptional Activation ◽  
Lactate Production ◽  
Luciferase Reporter ◽  
Transcriptional Level ◽  
Atp Production ◽  
Reporter Assays

Abstract Background Polo-like kinase 3 (PLK3) has been documented as a tumor suppressor in several types of malignancies. However, the role of PLK3 in colorectal cancer (CRC) progression and glucose metabolism remains to be known. Methods The expression of PLK3 in CRC tissues was determined by immunohistochemistry. Cells proliferation was examined by EdU, CCK-8 and in vivo analyses. Glucose metabolism was assessed by detecting lactate production, glucose uptake, mitochondrial respiration, extracellular acidification rate, oxygen consumption rate and ATP production. Chromatin immunoprecipitation, luciferase reporter assays and co-immunoprecipitation were performed to explore the signaling pathway. Specific targeting by miRNAs was determined by luciferase reporter assays and correlation with target protein expression. Results PLK3 was significantly downregulated in CRC tissues and its low expression was correlated with worse prognosis of patients. In vitro and in vivo experiments revealed that PLK3 contributed to growth inhibition of CRC cells. Furthermore, we demonstrated that PLK3 impeded glucose metabolism via targeting Hexokinase 2 (HK2) expression. Mechanically, PLK3 bound to Heat shock protein 90 (HSP90) and facilitated its degradation, which led to a significant decrease of phosphorylated STAT3. The downregulation of p-STAT3 further suppressed the transcriptional activation of HK2. Moreover, our investigations showed that PLK3 was directly targeted by miR-106b at post-transcriptional level in CRC cells. Conclusion This study suggests that PLK3 inhibits glucose metabolism by targeting HSP90/STAT3/HK2 signaling and PLK3 may serve as a potential therapeutic target in colorectal cancer.

scholarly journals FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Weixing Dai ◽  
Xianke Meng ◽  
Shaobo Mo ◽  
Wenqiang Xiang ◽  
Ye Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Underlying Mechanism ◽  
Low Expression

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.

scholarly journals Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1277 ◽  
Author(s):  
Takao Tsurubuchi ◽  
Makoto Shirakawa ◽  
Wataru Kurosawa ◽  
Kayo Matsumoto ◽  
Risa Ubagai ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Cultured Cells ◽  
Tumor Model ◽  
Intracellular Distribution ◽  
Inductively Coupled ◽  
Inductively Coupled Mass Spectrometry ◽  
Icp Ms ◽  
High Concentrations

Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as 10B delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient 10B concentration within tumors. To address the issue of 10B accumulation and retention in tumor tissue, we developed MMT1242, a novel boron-containing α-d-mannopyranoside. We evaluated the uptake, intracellular distribution, and retention of MMT1242 in cultured cells and analyzed biodistribution, tumor-to-normal tissue ratio and toxicity in vivo. Fluorescence imaging using nitrobenzoxadiazole (NBD)-labeled MMT1242 and inductively coupled mass spectrometry (ICP-MS) were performed. The effectiveness of BNCT using MMT1242 was assessed in animal irradiation studies at the Kyoto University Research Reactor. MMT1242 showed a high uptake and broad intracellular distribution in vitro, longer tumor retention compared to BSH and BPA, and adequate tumor-to-normal tissue accumulation ratio and low toxicity in vivo. A neutron irradiation study with MMT1242 in a subcutaneous murine tumor model revealed a significant tumor inhibiting effect if injected 24 h before irradiation. We therefore report that 10B-MMT1242 is a candidate for further clinical BNCT studies.

Sign in / Sign up

Export Citation Format

Share Document