AEROBIC GLYCOLYSIS OF X-IRRADIATED THYMOCYTES

1963 ◽  
Vol 41 (1) ◽  
pp. 2157-2169 ◽  
Author(s):  
Kimiko Araki ◽  
D. K. Myers

The aerobic lactate production of rat thymocyte suspensions incubated at 37 °C for 2 hours was doubled following exposure to approximately 70 r X-radiation. Lower doses down to 18 r also produced a significant increase in aerobic lactate production. Increased lactate accumulation following exposure to 1000 r was observed after incubation for as little as 30–60 minutes, though the rate of accumulation increased still further between 2 and 4 hours incubation. A decrease in pH or temperature during incubation of irradiated thymocyte suspensions minimized the lactic acid accumulation. A comparison of the effects of X-irradiation in different media and of the effects of several metabolic inhibitors suggested that the increase in aerobic lactate production was a sensitive indicator of cell damage associated with the loss of intracellular potassium ions.Respiration and anaerobic glycolysis of the thymus cells were both much less sensitive than aerobic glycolysis to the effects of X-irradiation. The "anaerobic" lactate production of rat thymocyte suspensions in the presence of dinitrophenol was reduced by 50% after exposure to 5000–6000 r of X-radiation.

1963 ◽  
Vol 41 (10) ◽  
pp. 2157-2169 ◽  
Author(s):  
Kimiko Araki ◽  
D. K. Myers

The aerobic lactate production of rat thymocyte suspensions incubated at 37 °C for 2 hours was doubled following exposure to approximately 70 r X-radiation. Lower doses down to 18 r also produced a significant increase in aerobic lactate production. Increased lactate accumulation following exposure to 1000 r was observed after incubation for as little as 30–60 minutes, though the rate of accumulation increased still further between 2 and 4 hours incubation. A decrease in pH or temperature during incubation of irradiated thymocyte suspensions minimized the lactic acid accumulation. A comparison of the effects of X-irradiation in different media and of the effects of several metabolic inhibitors suggested that the increase in aerobic lactate production was a sensitive indicator of cell damage associated with the loss of intracellular potassium ions.Respiration and anaerobic glycolysis of the thymus cells were both much less sensitive than aerobic glycolysis to the effects of X-irradiation. The "anaerobic" lactate production of rat thymocyte suspensions in the presence of dinitrophenol was reduced by 50% after exposure to 5000–6000 r of X-radiation.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
N. Gurukripa Kowlgi ◽  
Lovely Chhabra

D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs primarily in individuals who have a history of short bowel syndrome. The unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic acid among other organic acids. The acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, hence giving rise to a vicious cycle. D-lactic acid accumulation in the blood can cause neurologic symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a combination of clinical and laboratory data including special assays for D-lactate. Treatment includes correcting the acidosis and decreasing substrate for D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to clear colonic flora. Although newer techniques for diagnosis and treatment are being developed, clinical diagnosis still holds paramount importance, as there can be many confounders in the diagnosis as will be discussed subsequently.


1959 ◽  
Vol XXXII (II) ◽  
pp. 151-166 ◽  
Author(s):  
François Matray ◽  
Danièle Gautheron

ABSTRACT The effects of adrenaline or corticotrophin (ACTH) injections 45–50 minutes before autopsy, have been compared on the metabolism of the isolated uterus from mature rats < 100 g, or ovariectomized adults and immature rats pretreated with oestradiol. According to the incubation medium of the uterus, the observed effects differ. While adrenaline causes a decrease of the Qo2 of the uterus in every studied case, whether the medium contains an added substrate or not, ACTH never diminishes the oxygen uptake of the uterus; moreover, an increase of the respiration of the uterus is observed after ACTH injections, when the rats have been pretreated with oestradiol (immature or castrates) and only when the incubation medium contains glucose (2 mg/ml); one observes a synergism between the action of oestrogens and the pituitary-adrenocortical system. The effects of ACTH and adrenaline on glycolysis are always different. ACTH does not alter the anaerobic glycolysis, while adrenaline decreases it (—25 %). Adrenaline increases the lactic acid present in the muscle at the moment of the death of the rat, and decreases the aerobic glycolysis (Krebs-Ringer phosphate with or without added glucose, Krebs-Ringer bicarbonate without glucose) except if the incubation medium is a Krebs-Ringer bicarbonate with glucose; then the glycolysis is unchanged. ACTH does not change the lactic acid present in the uterus when the animal is killed. When incubated in a Krebs-Ringer phosphate, uteri of ACTH treated rats have a significant glycolysis; if glucose is added to the medium the glycolysis in uteri of oestradiol pretreated immature rats is increased by 30 % under the influence of ACTH injections. But, when the uteri are incubated in a Krebs-Ringer bicarbonate medium, ACTH has no effect on the aerobic glycolysis, if no glucose is added, but diminishes it when glucose is added to the medium. Adrenaline injections enhance the output of lactic acid from the muscle.


1939 ◽  
Vol 127 (849) ◽  
pp. 576-583 ◽  

During the last few years various lines of work have suggested a relationship between carbohydrate metabolism and organizer phenomena (cf. the reviews of Weiss (1935), Needham (1936), and Spemann (1938)). Manometric studies of carbohydrate breakdown are therefore desirable and these became possible with the development of the Cartesian diver ultramicromanometer. The recent investigations of Boell, Needham and Rogers (1939), using this technique, showed that in the amphibian gastrula the dorsal lip region has a higher anaerobic glycolysis than the ventral ectoderm. The work to be described in this paper is an attempt to adapt the diver manometer to the measurement of aerobic glycolysis, and to find out whether a similar regional difference exists in aerobic glycolysis. Owing to the technical difficulty, no previous attempts have been made to measure the Q O L 2 of parts of the gastrula, although measurements of lactic acid production in air and in nitrogen of whole eggs have been made by Brachet (1934) and Lennerstand (1933). Their results as regard aerobic glycolysis are in close agreement; in the gastrula stage a Q O L 2 of about + 0·05 being found. Since in both of these investigations the methods used were relatively crude, they could give no indication of regional differences.


2021 ◽  
Vol 17 (1) ◽  
pp. e1009122
Author(s):  
Hendrik Possemiers ◽  
Leen Vandermosten ◽  
Philippe E. Van den Steen

Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can aggravate the outcome of malaria. Despite its clear association with mortality in malaria patients, the etiology of lactic acidosis is not completely understood. In this review, the possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. The increased lactate production is caused by several factors, including the metabolism of intraerythrocytic Plasmodium parasites, aerobic glycolysis by activated immune cells, and an increase in anaerobic glycolysis in hypoxic cells and tissues as a consequence of parasite sequestration and anemia. Impaired hepatic and renal lactate clearance, caused by underlying liver and kidney disease, might further aggravate hyperlactatemia. Multiple factors thus participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance.


1959 ◽  
Vol 14 (3) ◽  
pp. 158-168 ◽  
Author(s):  
Francesco Bresciani ◽  
Klaus Dose ◽  
Boris Rajewsky

I. X-irradiation of isolated rat diaphragm with 10 to 200 kr produces a change in tissue metabolism which we schematize in two successive phases:1st phase: Increase of oxygen comsumption, proportional to the dosage; an even greater increase of CO2 production; QCO2/QO2 > 1, that is, aerobic glycolysis; inhibition of anaerobic glycolysis.2nd phase: Reduction of oxygen consumption, proportional to the dosage (over 65 kr the Qo2 decreases below the control); an even greater decrease of CO2 production: QCO2/QO2 > 1; a greater inhibition of anaerobic glycolysis.With 200 kr or more no increase of respiration appears, but instead from the beginning there is a reduction of the metabolism as described in the second phase.II. A similar effect is found in rat liver and in frog heart tissue.III. When the tissue was incubated in the homologus serum no change in the quality of the described effect was observed. Under our experimental conditions the tissue was X-irradiated within a small quantity of incubation medium and immediately afterwards placed in a fresh medium; this limits the effect of oxidative radicals (arising in the X-irradiated water) upon the tissue.IV. We set forth the experimental hypothesis that all the described changes in the metabolism of the cell after X-irradiation depend upon a primary alteration of electrolyte balance in the cell, especially of the potassium/sodium relationship. The well known decrease of glycolysis after X-irradiation is a consequence of the loss of potassium from the X-irradiated cell.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ling Mao ◽  
Xiaoweng Wu ◽  
Zhengpeng Gong ◽  
Ming Yu ◽  
Zhi Huang

Abstract Background/objective Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC). Methods The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively. Results A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells. Conclusion This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ling Jin ◽  
Eun-Yeong Kim ◽  
Tae-Wook Chung ◽  
Chang Woo Han ◽  
So Young Park ◽  
...  

AbstractMost cancer cells primarily produce their energy through a high rate of glycolysis followed by lactic acid fermentation even in the presence of abundant oxygen. Pyruvate dehydrogenase kinase (PDK) 1, an enzyme responsible for aerobic glycolysis via phosphorylating and inactivating pyruvate dehydrogenase (PDH) complex, is commonly overexpressed in tumors and recognized as a therapeutic target in colorectal cancer. Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata Bunge (Compositae). Here, we report that HsA is a PDK1 inhibitor can reduce the growth of colorectal cancer and consequent activation of mitochondrial ROS-dependent apoptotic pathway both in vivo and in vitro. Computational simulation and biochemical assays showed that HsA directly binds to the lipoamide-binding site of PDK1, and subsequently inhibits the interaction of PDK1 with the E2 subunit of PDH complex. As a result of PDK1 inhibition, lactate production was decreased, but oxygen consumption was increased. Mitochondrial ROS levels and mitochondrial damage were also increased. Consistent with these observations, the apoptosis of colorectal cancer cells was promoted by HsA with enhanced activation of caspase-3 and -9. These results suggested that HsA might be a potential candidate for developing a novel anti-cancer drug through suppressing cancer metabolism.


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