scholarly journals The inhibitory effect at the hexokinase level of disulphides on glucose metabolism in human erythrocytes

1962 ◽  
Vol 84 (2) ◽  
pp. 286-291 ◽  
Author(s):  
L ELDJARN ◽  
J BREMER
1986 ◽  
Vol 86 (1) ◽  
pp. 57-67
Author(s):  
G. Lelkes ◽  
I. Fodor ◽  
G. Lelkes ◽  
S.R. Hollan

It has previously been shown that reversible intramembrane particle aggregation can be induced in non-haemolysed human erythrocytes. This phenomenon, which can be induced by the cationic dye Acridine Orange, has been further investigated using different experimental conditions that are expected to influence the rate of aggregation of the particles. In addition to the concentration of the dye, the rate of aggregation was also found to be dependent on the extracellular and intracellular pH, as well as on the type of buffer used. While lowering the pH of the Acridine Orange solutions resulted in decreased particle clustering, low intracellular pH increased and elevated intracellular pH decreased particle aggregation. Furthermore, at a given dye concentration and a given pH, Acridine Orange caused more intense aggregation in Tris-buffered saline than in isotonic phosphate buffer or phosphate-buffered saline. Under appropriate conditions Acridine Orange caused significant particle aggregation at concentrations as low as 0.25 mM within 30 s. During this period only discocyte-stomatocyte transformation occurred; neither agglutination nor vesiculation of the erythrocytes could be detected. Treatment of the erythrocytes with Diamide (Serva), which cross-links spectrin via disulphide bridges and thereby reduces lateral diffusion of integral membrane proteins over large distances, had no inhibitory effect on Acridine-Orange-induced particle aggregation. Heating the erythrocytes to 50 degrees C, at which temperature denaturation of spectrin and fragmentation of the erythrocytes occur, and subsequently incubating them in Acridine Orange at room temperature, caused an almost maximal rate of particle aggregation within 10–30 s, without haemolysis. The possible mechanism and significance of the particle aggregation phenomenon are discussed.


1968 ◽  
Vol 46 (5) ◽  
pp. 445-450 ◽  
Author(s):  
S. V. Manohar ◽  
M. H. Lerner ◽  
D. Rubinstein

Incubation of human erythrocytes with glucose and 1.5 mM adenine for 12 h doubles the intracellular level of ATP because of synthesis of the nucleotide from the purine. The effect of the nucleosides inosine, guanosine, and adenosine on the synthesis of nucleotide labile phosphate during the incubation was studied. Inosine and guanosine had no effect, but adenosine, in concentrations between 10 and 20 mM, inhibited the increase in labile phosphate and the incorporation of adenine-8-14C into ATP. The adenosine has no effect on the slight incorporation of adenine-8-14C into, or the intracellular concentration of, ADP or AMP. The inhibition is not due to the formation of ammonia and (or) inosine resulting from the deamination of adenosine, nor is it due to the change of pH produced by the ammonia. Adenosine must be present to produce its inhibitory effect and the inhibition can be reversed by removal of the nucleoside, either by washing the cells or through the action of the erythrocyte adenosine deaminase. It thus appears that adenosine produces its effect when it is present in concentrations too great to be completely deaminated. A small proportion (0.5%) of the added adenosine is incorporated into the cellular nucleotides, more than half into IMP, resulting in a marked increase in the concentration of this nucleotide. It is suggested that adenosine acts by inhibition of the synthesis of either 5-phosphoribosyl-1-pyrophosphate or adenylic acid.


1962 ◽  
Vol 41 (7) ◽  
pp. 1446-1453 ◽  
Author(s):  
G. Fornaini ◽  
G. Leoncini ◽  
L. Luzzatto ◽  
G. Segni

Oncogene ◽  
2019 ◽  
Vol 39 (2) ◽  
pp. 469-485 ◽  
Author(s):  
Yu Liang ◽  
Lidan Hou ◽  
Linjing Li ◽  
Lei Li ◽  
Liming Zhu ◽  
...  

Abstract The development of chemoresistance remains a major challenge that accounts for colorectal cancer (CRC) lethality. Dichloroacetate (DCA) was originally used as a metabolic regulator in the treatment of metabolic diseases; here, DCA was assayed to identify the mechanisms underlying the chemoresistance of CRC. We found that DCA markedly enhanced chemosensitivity of CRC cells to fluorouracil (5-FU), and reduced the colony formation due to high levels of apoptosis. Using the microarray assay, we noted that miR-149-3p was involved in the chemoresistance of CRC, which was modulated by wild-type p53 after DCA treatment. In addition, PDK2 was identified as a direct target of miR-149-3p. Mechanistic analyses showed that overexpression of miR-149-3p enhanced 5-FU-induced apoptosis and reduced glucose metabolism, similar to the effects of PDK2 knockdown. In addition, overexpression of PDK2 partially reversed the inhibitory effect of miR-149-3p on glucose metabolism. Finally, both DCA treatment and miR-149-3p overexpression in 5-FU-resistant CRC cells were found to markedly sensitize the chemotherapeutic effect of 5-FU in vivo, and this effect was also validated in a small retrospective cohort of CRC patients. Taken together, we determined that the p53/miR-149-3p/PDK2 signaling pathway can potentially be targeted with DCA treatment to overcome chemoresistant CRC.


2018 ◽  
Vol 70 ◽  
pp. 92-96 ◽  
Author(s):  
Haruaki Kitagawa ◽  
Saeki Miki-Oka ◽  
Gen Mayanagi ◽  
Yuki Abiko ◽  
Nobuhiro Takahashi ◽  
...  

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