scholarly journals Toxic effect of puromycin on erythrocyte membranes which is unrelated to inhibition of protein synthesis

Blood ◽  
1975 ◽  
Vol 45 (1) ◽  
pp. 21-27 ◽  
Author(s):  
ER Burka ◽  
SK Ballas ◽  
SM Sabesin

Abstract Exposure of rabbit or human erythrocytes to concentrations of puromycin as low as 7 x 10(-4)M for 2 hr causes damage to the cell membrane, as evidenced by increased susceptibility of the cells to hyposmotic lysis, increased cell rigidity, and ultrastructural changes consistent with severe membrane damage. Puromycin causes a concentration-dependent internalization of the erythrocyte membrane, resulting in vacuolization of the cells, at concentrations between 7 x 10(-4) M and 10(-2) M. Since the erythrocyte does not synthesize protein, the data indicate that puromycin has a direct toxic effect on erythroid cell membranes which is unrelated to its action in inhibiting the synthesis of protein.

Blood ◽  
1975 ◽  
Vol 45 (1) ◽  
pp. 21-27
Author(s):  
ER Burka ◽  
SK Ballas ◽  
SM Sabesin

Exposure of rabbit or human erythrocytes to concentrations of puromycin as low as 7 x 10(-4)M for 2 hr causes damage to the cell membrane, as evidenced by increased susceptibility of the cells to hyposmotic lysis, increased cell rigidity, and ultrastructural changes consistent with severe membrane damage. Puromycin causes a concentration-dependent internalization of the erythrocyte membrane, resulting in vacuolization of the cells, at concentrations between 7 x 10(-4) M and 10(-2) M. Since the erythrocyte does not synthesize protein, the data indicate that puromycin has a direct toxic effect on erythroid cell membranes which is unrelated to its action in inhibiting the synthesis of protein.


Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 189-195 ◽  
Author(s):  
TA Lane ◽  
SK Ballas ◽  
ER Burka

Abstract Human reticulocytes are capable of synthesizing membrane lipids from 14C-glycerol de novo. In both sickle and nonsickle reticulocytes the majority of 14C-glycerol was incorporated into phospholipids, primarily phosphatidylserine and phosphatidylcholine. Incorporation into sphingomyelin was minimal. The most abundant neutral lipid synthesized was triglyceride. In the absence of sickling, the rate of lipid synthesis in sickle reticulocytes was similar to that of nonsickle reticulocytes. With the induction of sickling under anoxic conditions sickle reticulocytes showed a prompt increase in the rate of lipid synthesis to an average of 69% above control values, while nonsickle reticulocytes under similar conditions decreased the rate of lipid synthesis. An increase in the rate of membrane lipid synthesis is associated in the mammalian erythroid cell with cell membrane damage. The findings further confirm that lesions of the erythroid cell membrane in sickle cell anemia are secondary to the sickling process itself.


1981 ◽  
Vol 59 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
R. P. Moody ◽  
P. Weinberger ◽  
R. Greenhalgh ◽  
A. Massalski

The algicidal properties of Aerotex 3470, a pesticide cosolvent in several fenitrothion formulations, have been investigated under controlled laboratory conditions. Aerotex (1–100 ppm) inhibited the growth of three unicellular freshwater algae (Chlamydomonas reinhardii, Chlorella pyrenoidosa, and Scenedesmus obtusiusculus) on agar plates and in liquid culture. Prolongation of the lag phase was directly related to Aerotex concentration. Algal cultures exposed for 1 h to Aerotex (1–10 ppm) had significantly reduced ATP levels. In all cases (agar, liquid culture, and ATP bioassays), Chlamydomonas and Chlorella were more sensitive to Aerotex than Scenedesmus.Electron microscopy demonstrated gross ultrastructural changes in Chlamydomonas treated for 1 h with Aerotex (5 ppm), including swollen mitochondria, disorganization of thylakoids, and crenulation of the cell membrane. Similar membrane damage was caused by 1-methylnaphthalene (5 ppm), a constituent of Aerotex.


Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 189-195
Author(s):  
TA Lane ◽  
SK Ballas ◽  
ER Burka

Human reticulocytes are capable of synthesizing membrane lipids from 14C-glycerol de novo. In both sickle and nonsickle reticulocytes the majority of 14C-glycerol was incorporated into phospholipids, primarily phosphatidylserine and phosphatidylcholine. Incorporation into sphingomyelin was minimal. The most abundant neutral lipid synthesized was triglyceride. In the absence of sickling, the rate of lipid synthesis in sickle reticulocytes was similar to that of nonsickle reticulocytes. With the induction of sickling under anoxic conditions sickle reticulocytes showed a prompt increase in the rate of lipid synthesis to an average of 69% above control values, while nonsickle reticulocytes under similar conditions decreased the rate of lipid synthesis. An increase in the rate of membrane lipid synthesis is associated in the mammalian erythroid cell with cell membrane damage. The findings further confirm that lesions of the erythroid cell membrane in sickle cell anemia are secondary to the sickling process itself.


1990 ◽  
Vol 17 (3) ◽  
pp. 224-227
Author(s):  
Henning F. Bjerregaard

The aim of the present study was to investigate the site and mode of trifluoperazine (TFP) action on cell membrane transport by the use of isolated frog skin. This cellular system gives access to the apical (outer) and basolateral (inner) membranes of the polarised epithelial cells. Both apical and basolateral TFP addition induced a dose-dependent stimulation of Na transport, and depolarised the cellular potential. The data indicate that TFP acts by increasing the Na permeability of the apical membrane. However, the mechanisms localised in the apical and basolateral membranes are quite different. Basolateral TFP addition increased Na transport due to a stimulation of PGE2 synthesis, whereas apical TFP addition abolished Na inhibition of the apical Na channels, and thereby enhanced the Na transport. An acute toxic effect on the electrophysiological parameters was noted after addition of high apical TFP concentrations (50–100μM). This toxic effect was dependent on the presence of Na in the apical solution.


2002 ◽  
Vol 11 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Shahida Shahana ◽  
Caroline Kampf ◽  
Godfried M. Roomans

Background: Allergic asthma is associated with an increased number of eosinophils in the airway wall. Eosinophils secrete cationic proteins, particularly major basic protein (MBP).Aim: To investigate the effect of synthetic cationic polypeptides such as poly-L-arginine, which can mimic the effect of MBP, on airway epithelial cells.Methods: Cultured airway epithelial cells were exposed to poly-L-arginine, and effects were determined by light and electron microscopy.Results: Poly-L-arginine induced apoptosis and necrosis. Transmission electron microscopy showed mitochondrial damage and changes in the nucleus. The tight junctions were damaged, as evidenced by penetration of lanthanum. Scanning electron microscopy showed a damaged cell membrane with many pores. Microanalysis showed a significant decrease in the cellular content of magnesium, phosphorus, sodium, potassium and chlorine, and an increase in calcium. Plakoglobin immunoreactivity in the cell membrane was decreased, indicating a decrease in the number of desmosomes.Conclusions: The results point to poly-L-arginine induced membrane damage, resulting in increased permeability, loss of cell-cell contacts and generalized cell damage.


1980 ◽  
Vol 87 (3) ◽  
pp. 828-832 ◽  
Author(s):  
K Sandvig ◽  
S Olsnes

At neutral pH, NH4Cl and chloroquine protected cells against diphtheria toxin. A brief exposure of the cells to low pH (4.5-5.5) at 37 degrees completely abolished this protection. When, to cells preincubated with diphtheria toxin and NH4Cl, neutralizing amounts of anti-diphtheria toxin were added before the pH was lowered, the toxic effect was considerably reduced, but it was not completely abolished. A much stronger toxic effect was seen when antibodies were added immediately after incubation at low pH. Upon a short incubation with diphtheria toxin at low pH, the rate of protein synthesis in the cells decreased much faster than when the normal pH was maintained. The data suggest that, at low pH, diphtheria toxin (or its A fragment) penetrates directly through the surface membrane of the cell. The possibility is discussed that, when the medium has a neutral pH, the entry of diphtheria toxin involves adsorptive endocytosis and reduction of the pH in the vesicles possibly by fusion with lysosomes. Low pH did not facilitate the entry of the closely related toxins abrin, ricin, and modeccin.


2021 ◽  
Vol 22 (2) ◽  
pp. 515
Author(s):  
Jaroslaw Szczepaniak ◽  
Joanna Jagiello ◽  
Mateusz Wierzbicki ◽  
Dorota Nowak ◽  
Anna Sobczyk-Guzenda ◽  
...  

The development of nanotechnology based on graphene and its derivatives has aroused great scientific interest because of their unusual properties. Graphene (GN) and its derivatives, such as reduced graphene oxide (rGO), exhibit antitumor effects on glioblastoma multiforme (GBM) cells in vitro. The antitumor activity of rGO with different contents of oxygen-containing functional groups and GN was compared. Using FTIR (fourier transform infrared) analysis, the content of individual functional groups (GN/exfoliation (ExF), rGO/thermal (Term), rGO/ammonium thiosulphate (ATS), and rGO/ thiourea dioxide (TUD)) was determined. Cell membrane damage, as well as changes in the cell membrane potential, was analyzed. Additionally, the gene expression of voltage-dependent ion channels (clcn3, clcn6, cacna1b, cacna1d, nalcn, kcne4, kcnj10, and kcnb1) and extracellular receptors was determined. A reduction in the potential of the U87 glioma cell membrane was observed after treatment with rGO/ATS and rGO/TUD flakes. Moreover, it was also demonstrated that major changes in the expression of voltage-dependent ion channel genes were observed in clcn3, nalcn, and kcne4 after treatment with rGO/ATS and rGO/TUD flakes. Furthermore, the GN/ExF, rGO/ATS, and rGO/TUD flakes significantly reduced the expression of extracellular receptors (uPar, CD105) in U87 glioblastoma cells. In conclusion, the cytotoxic mechanism of rGO flakes may depend on the presence and types of oxygen-containing functional groups, which are more abundant in rGO compared to GN.


2021 ◽  
Author(s):  
Delaram Poormoghadam ◽  
Bita Rasoulian Shiadeh ◽  
Fereshte Azedi ◽  
Hani Tavakol ◽  
Seyed Mahdi Rezayat ◽  
...  

Abstract Spinal cord injury (SCI) is a debilitating condition for which no definitive treatment has yet been identified. Noteworthy, it influences other tissues through inflammatory reactions and metabolic disturbance. Therefore, fingolimod (FTY-720) as an FDA-approved inflammatory modulator would be promising. In the present study, nanocarriers at two distinct monodisperse particle sizes of 60 (nF60) and 190 (nF190) nm were prepared.The neural stem cell (NSC) viability and LDH release were studied in the face of the nanocarriers and free FTY-720. Results indicated that nanocarriers and free FTY-720 enhanced NSC viability than the control group.However, nF190 significantly induced less cell membrane damage than nF60. Nanocarriers and free FTY-720 enhanced motor neuron recovery in SCI rats, while body weight and return to bladder reflux by nF190 was significantly higher than nF60 groups. Return to bladder reflux might be due to the role of FTY-720 in regulation of detrusor muscle tone and preservation of the integrity of vessels by acting on endothelial cells. Moreover,nF190 gained higher soleus muscle weight than the free drugs;probably decreasing pro-inflammatory cytokines in soleus diminish muscular atrophy in SCI rats.To sum thing up, larger nanacarrirs with less cell membrane damage seems to be more efficient than smaller ones to manage SCI.


1981 ◽  
Vol 49 (1) ◽  
pp. 369-382
Author(s):  
S. Fujikawa

Human erythrocytes suspended in buffered isotonic saline were frozen to the temperature of liquid nitrogen at various cooling rates of 3, 140, 700, 1800, 3500, 8000 and 11 500 deg. C/min. The membrane ultrastructure in the frozen state and the extent of haemolysis after thawing were examined at each cooling rate. As the cooling rates increased from 3 to 3500 deg. C/min, the extent of lysis gradually decreased, but further increase in cooling rates in excess of 8000 deg. C/min resulted in an abrupt increase of lysis. Membrane-associated vesicles devoid of intramembrane particles (IMPs) were formed in the erythrocyte membranes frozen at cooling rates slower than 1800 deg. C/min. The frequency and size of these vesicles were highly cooling-rate-dependent and they were no longer formed in the erythrocyte membranes frozen at cooling rates faster than 3500 deg. C/min. Another membrane ultrastructural change associated closely with the formation of intracellular ice crystals appeared at cooling rates faster than 8000 deg. C/min. The membrane regions in direct contact with intracellular ice crystals were physically damaged and had an appearance resembling worm-eaten spots. The erythrocytes frozen at a cooling rate of 3500 deg. C/min exhibited ultrastructural integrity of the membrane by avoiding the membrane changes caused by either slow or fast freezing. It is suggested, from the close relation between membrane ultrastructure and the extent of haemolysis, that the ultrastructural integrity of membrane in the frozen state is important for avoiding haemolysis after thawing, and that the membrane ultrastructural changes caused by both slow and fast freezing were responsible for the lysis after thawing.


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