LOVASTATIN-INDUCED CARDIAC CELL DEATH IS MEDIATED THROUGH INHIBITION OF PROTEIN SYNTHESIS.

Abstract Programmed cell death is a dynamic and critical mechanism of cell suicide in eukaryotes and prokaryotes. MazF is a ribonuclease protein involved in bacterial intracellular programmed death. This protein cleaves mRNAs at ACA sequences, leading to inhibition of protein synthesis and triggering cell death. Given that cancer is heterogenic and has varied susceptibility to treatment, we examined the impact of MazF proteins on the growth and viability of three cancer cell lines: MCF7, HT29, and AGS. These cell lines were transfected with ACA-less mazF mRNAs and evaluated for MazF-mediated cell death. The data illustrated that efficient MazF translation leads to a significant reduction in cell viability and is modulated by structural elements of ACA-less mazF mRNAs. In the presence of MazF, the levels of activated caspase-3 and -7 were significantly elevated in transfected cells, confirming the occurrence of apoptosis. We also quantified mRNA translation on a single-cell basis in MCF7 and AGS cell lines to examine MazF-mediated inhibition of protein synthesis. MazF expression significant decreases the levels of protein translation in the examined cell lines. This is the first report of MazF as a potential anti-cancer agent via induction of apoptosis in MCF7, AGS, and HT-29 cell lines.

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Intracellular Transport and Cytotoxicity of the Protein Toxin Ricin

Toxins ◽

10.3390/toxins11060350 ◽

2019 ◽

Vol 11 (6) ◽

pp. 350 ◽

Cited By ~ 14

Author(s):

Natalia Sowa-Rogozińska ◽

Hanna Sominka ◽

Jowita Nowakowska-Gołacka ◽

Kirsten Sandvig ◽

Monika Słomińska-Wojewódzka

Keyword(s):

Cell Death ◽

Protein Synthesis ◽

Host Cell ◽

Intracellular Transport ◽

Ricinus Communis ◽

Yeast Cells ◽

Protein Toxin ◽

Inhibition Of Protein Synthesis ◽

A Chain ◽

Golgi Network

Ricin can be isolated from the seeds of the castor bean plant (Ricinus communis). It belongs to the ribosome-inactivating protein (RIP) family of toxins classified as a bio-threat agent due to its high toxicity, stability and availability. Ricin is a typical A-B toxin consisting of a single enzymatic A subunit (RTA) and a binding B subunit (RTB) joined by a single disulfide bond. RTA possesses an RNA N-glycosidase activity; it cleaves ribosomal RNA leading to the inhibition of protein synthesis. However, the mechanism of ricin-mediated cell death is quite complex, as a growing number of studies demonstrate that the inhibition of protein synthesis is not always correlated with long term ricin toxicity. To exert its cytotoxic effect, ricin A-chain has to be transported to the cytosol of the host cell. This translocation is preceded by endocytic uptake of the toxin and retrograde traffic through the trans-Golgi network (TGN) and the endoplasmic reticulum (ER). In this article, we describe intracellular trafficking of ricin with particular emphasis on host cell factors that facilitate this transport and contribute to ricin cytotoxicity in mammalian and yeast cells. The current understanding of the mechanisms of ricin-mediated cell death is discussed as well. We also comment on recent reports presenting medical applications for ricin and progress associated with the development of vaccines against this toxin.

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Properties of a Revertant of Escherichia coli Viable in the Presence of Spermidine Accumulation: Increase in l-Glycerol 3-Phosphate

Journal of Bacteriology ◽

10.1128/jb.183.15.4493-4498.2001 ◽

2001 ◽

Vol 183 (15) ◽

pp. 4493-4498 ◽

Cited By ~ 10

Author(s):

V. Samuel Raj ◽

Hideyuki Tomitori ◽

Madoka Yoshida ◽

Auayporn Apirakaramwong ◽

Keiko Kashiwagi ◽

...

Keyword(s):

Escherichia Coli ◽

Cell Death ◽

Protein Synthesis ◽

Glycerol Kinase ◽

High Concentration ◽

Gene Encoding ◽

E Coli ◽

Inhibition Of Protein Synthesis ◽

High Concentrations ◽

Ribosome Modulation Factor

ABSTRACT Escherichia coli CAG2242 cells are deficient in thespeG gene encoding spermidine acetyltransferase. When these cells were cultured in the presence of 0.5 to 4 mM spermidine, their viability was greatly decreased through the inhibition of protein synthesis by overaccumulation of spermidine. When the cells were cultured with a high concentration of spermidine (4 mM), a revertant strain was obtained. We found that a 55-kDa protein, glycerol kinase, was overexpressed in the revertant and that synthesis of a ribosome modulation factor and the RNA polymerase ς38 subunit, factors important for cell viability, was increased in the revertant. Levels of l-glycerol 3-phosphate also increased in the revertant. Transformation of glpFK, which encodes a glycerol diffusion facilitator (glpF) and glycerol kinase (glpK), to E. coli CAG2242 partially prevented the cell death caused by accumulation of spermidine. It was also found that l-glycerol 3-phosphate inhibited spermidine binding to ribosomes and attenuated the inhibition of protein synthesis caused by high concentrations of spermidine. These results indicate that l-glycerol 3-phosphate reduces the binding of excess amounts of spermidine to ribosomes so that protein synthesis is recovered.

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