scholarly journals Rapid induction of apoptosis by deregulated uptake of polyamine analogues

1997 ◽  
Vol 328 (1) ◽  
pp. 307-316 ◽  
Author(s):  
Rei-Huang HU ◽  
E. Anthony PEGG
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Oxidation Products ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Polyamine Biosynthesis ◽  
Polyamine Analogues ◽  
Induction Of Apoptosis

Treatment of Chinese hamster ovary cells with α-difluoromethylornithine for 3 days, followed by exposure to cycloheximide, led to an unregulated, rapid and massive accumulation of polyamine analogues. This accumulation led to cell death by apoptosis within a few hours. Clear evidence of DNA fragmentation was seen in response to both N-terminally ethylated polyamines and to polyamines containing methyl groups on the terminal carbon atoms. Programmed cell death was induced within 2-4 h of exposure to 1 μM or higher concentrations of N1,N11-bis(ethyl)norspermine. The presence of cycloheximide increased the uptake of the polyamine analogues and therefore led to cell death at lower analogue concentrations, but it was not essential for the induction of apoptosis, since similar effects were seen when the protein synthesis inhibitor was omitted and the concentration of N1,N11-bis(ethyl)norspermine was increased to 5 μM or more The induction of apoptosis was blocked both by the addition of the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, or by the addition of the polyamine oxidase inhibitor N1-methyl-N2-(2,3-butadienyl)butane-1,4-diamine (MDL 72,527). These experiments provide evidence to support the concepts that: (1) polyamines or their oxidation products may be initiators of programmed cell death; (2) regulation of polyamine biosynthesis and uptake prevents the accumulation of toxic levels of polyamines; and (3) the anti-neoplastic effects of bis(ethyl) polyamine analogues may be due to the induction of apoptosis in sensitive tumour cells.

scholarly journals Specific dose-dependent effects of ethane 1,2-dimethanesulfonate in rat and mouse Leydig cells and non-steroidogenic cells on programmed cell death

2004 ◽  
Vol 181 (1) ◽  
pp. 169-178 ◽  
Author(s):  
FF Rommerts ◽  
L Kuhne ◽  
GW van Cappellen ◽  
DM Stocco ◽  
SR King ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Leydig Cells ◽  
Morphological Changes ◽  
Chinese Hamster Ovary Cells ◽  
Fluorescent Microscopy ◽  
Chinese Hamster ◽  
Time Lapse ◽  
Dna Laddering ◽  
Steroidogenic Cell

The mechanism by which ethane 1,2-dimethanesulfonate (EDS) selectively kills Leydig cells is poorly understood. To characterize further the cell-specific actions of EDS, we studied biochemical and morphological changes during apoptosis in different Leydig cell and non-steroidogenic cell models.Rat testicular and H540 tumor Leydig cells were killed by 1-2 mM EDS, whereas 20 mM EDS were required for MA-10 cells. This higher concentration of EDS was also necessary for activation of apoptosis in non-steroidogenic Chinese hamster ovary cells, whereas COS-1 monkey kidney cells were resistant. These variable effects of EDS on apoptosis were independent of new protein synthesis and, interestingly, could be delayed by co-incubation with dibutyrl cyclic AMP. Along with cell death, we also observed chromosomal fragmentation and other hallmarks indicative of apoptosis as evidenced by DNA laddering and fluorescent microscopy. Time-lapse photography with a confocal microscope showed that the time of onset, duration and even the sequence of apoptotic events between individual H540 cells was heterogeneous. When the dose of EDS was gradually increased from 2 to 10 mM, the proportion of cells showing normal apoptotic features gradually decreased. Intriguingly, treatment with 10 mM EDS did not result in death for most cells and was marked by an absence of DNA laddering and ultrastructural features of apoptosis and necrosis. However, incubation with 20 mM EDS resulted in necrosis.These results demonstrated that the effects of EDS on cell survival are not specific to Leydig cells, that different cell types have different sensitivities to EDS and that stimulation of the cAMP pathway may mitigate EDS action. The data obtained with H540 cells further revealed that EDS can induce two types of programmed cell death.

scholarly journals Co-expression of MG29 and Ryanodine Receptor Leads to Apoptotic Cell Death

2004 ◽  
Vol 279 (19) ◽  
pp. 19387-19390 ◽  
Author(s):  
Zui Pan ◽  
Yutaka Hirata ◽  
Ramakrishnan Y. Nagaraj ◽  
Jiying Zhao ◽  
Miyuki Nishi ◽  
...  
Keyword(s):  
Cell Death ◽  
Ryanodine Receptor ◽  
Apoptotic Cell ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Bilayer Membrane ◽  
Apoptotic Cell Death ◽  
Functional Interaction ◽  
Release Channel ◽  
Intracellular Ca

Perturbation of intracellular Ca2+homeostasis has been shown to regulate the process of cell proliferation and apoptosis. Our previous studies show that mitsugumin 29 (MG29), a synaptophysin-related protein localized in the triad junction of skeletal muscle, serves an essential role in muscle Ca2+signaling by regulating the process of store-operated Ca2+entry. Here we report a functional interaction between MG29 and the ryanodine receptor (RyR)/Ca2+release channel. The purified MG29 protein enhances activity of the RyR/Ca2+release channel incorporated into the lipid bilayer membrane. Co-expression of MG29 and RyR in Chinese hamster ovary cells leads to apoptotic cell death resulting from depletion of intracellular Ca2+stores, despite neither protein expression alone exhibits any significant effect on cell viability. In transient expression studies, the presence of RyR in the endoplasmic reticulum leads to retention of MG29 from the plasma membrane into the intracellular organelles. This functional interaction between MG29 and RyR could have important implications in the Ca2+signaling processes of muscle cells. Our data also show that perturbation of intracellular Ca2+homeostasis can serve as a key signal in the initiation of apoptosis.

scholarly journals In vivo induction of apoptosis (programmed cell death) in mouse thymus by administration of lipopolysaccharide.

1993 ◽  
Vol 61 (12) ◽  
pp. 5044-5048 ◽  
Author(s):  
Y H Zhang ◽  
K Takahashi ◽  
G Z Jiang ◽  
M Kawai ◽  
M Fukada ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mouse Thymus ◽  
Induction Of Apoptosis ◽  
In Vivo Induction

scholarly journals Chinese hamster cells can be reversibly blocked before mitosis with the protein synthesis inhibitor, emetine

1983 ◽  
Vol 59 (1) ◽  
pp. 257-268
Author(s):  
J.T. Westwood ◽  
E.B. Wagenaar
Keyword(s):  
Protein Synthesis ◽  
Mitotic Index ◽  
Chinese Hamster ◽  
Inhibitory Effect ◽  
Eukaryotic Cells ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Chinese Hamster Cells ◽  
Initial Concentration ◽  
G2 Phase

The inhibition of protein synthesis in eukaryotic cells will prevent them from entering mitosis. Emetine inhibits peptide elongation. When it was added to asynchronous populations of Chinese hamster ovary (CHO) cells, the mitotic index decreased sharply 30 to 40 min later. It was found that the inhibitory effect of emetine could be reversed when it was removed and the reversibility was dependent on both the initial concentration of emetine and the pH of the medium. Cell populations that were blocked by emetine for up to 2h showed a four- to fivefold increase in mitotic index approximately 1 h after the emetine was removed. These results indicate that there is a point or period in G2 phase at which critical ‘mitotic proteins’ are being synthesized, and if their synthesis is interrupted cells will fail to enter mitosis.

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