Poly(A) polymerase activity in ethionine-intoxicated rats: the relative effectiveness of disaggregated and intact polyribosomes as primers for poly(A) polymerase

1980 ◽  
Vol 58 (3) ◽  
pp. 236-242 ◽  
Author(s):  
James Dennis ◽  
Robert Kisilevsky

Ethionine intoxication causes a change in the metabolism of poly(A) sequences on the 3′ OH terminus of mRNA in rat liver in vivo. In an attempt to determine the factors responsible for these changes, nuclear and cytoplasmic poly(A) polymerase activities and the state of the primer were examined in vitro. Requirements for optimal enzyme activities were determined. The nuclear and cytoplasmic enzymes had different K+, Mn2+, and poly(A) primer optima. The levels of nuclear and cytoplasmic poly(A) polymerase activity were shown to decrease following ethionine intoxication. Poly(A)+ RNA isolated from the livers of saline- and ethionine-treated rats served equally well as primers for the cytoplasmic poly(A) polymerase. Disaggregated polysomes were seven times more effective as primers than were intact polysomes. The results suggest that the mRNP particle which is released from polysomes as a result of ethionine intoxication functions better as a poly(A) polymerase primer than does the intact polysome.

1971 ◽  
Vol 125 (4) ◽  
pp. 943-952 ◽  
Author(s):  
B. W. Stewart ◽  
P. N. Magee

1. Administration of a single dose of dimethylnitrosamine to rats temporarily fed on a protein-deficient diet causes a high incidence of kidney tumours. The effect of such a dose of dimethylnitrosamine (40mg/kg body wt.) on metabolism of nucleic acids and protein in rat liver and kidneys was examined during the week immediately after administration. 2. Incorporation of [14C]leucine and [14C]orotate into hepatic macromolecules was inhibited within 5h of injection of dimethylnitrosamine, and did not recover for at least 5 days. Interpretation of these results is complicated by the concomitant extensive hepatic necrosis. 3. Renal RNA synthesis was assayed by incorporation of [14C]orotate in vivo and measurement of DNA-dependent RNA polymerase activity in vitro. Both systems indicate biphasic inhibition; minimal activity was recorded 9h and 3 days after treatment. Changes in incorporation of [14C]leucine into renal protein were similar but less marked. 4. Sucrose-density-gradient analysis of renal cytoplasmic RNA indicated increased synthesis of rRNA 24h after injection of the nitrosamine. The rate of loss of radioactivity from kidney ribosomes pre-labelled with [14C]orotate was not modified by dimethylnitrosamine. 5. Dimethylnitrosamine increased incorporation of [3H]-thymidine into renal DNA. The three distinct periods of stimulated synthesis observed are discussed, with particular reference to recently published morphological studies of the sequential development of kidney tumours induced by dimethylnitrosamine in protein-depleted rats.


1983 ◽  
Vol 18 ◽  
pp. 64
Author(s):  
C. Rhodes ◽  
C.R. Elcombe ◽  
M.D. Stonard ◽  
M.G. Simpson ◽  
A. Vernall

1972 ◽  
Vol 130 (2) ◽  
pp. 619-629 ◽  
Author(s):  
G. E. Neal

1. Aflatoxin B1, administered in vivo, inhibits the incorporation of [14C]orotic acid in vivo into rat liver nuclei, and also inhibits both Mg2+- and Mn2+-dependent RNA polymerase activities in nuclei assayed in vitro. 2. Aflatoxin B1 inhibits the cortisol-induced increase in incorporation of [14C]leucine in vivo, but does not affect the control value of this activity. 3. Aflatoxin B1 administered in vivo inhibits the increase in nuclear Mg2+-dependent RNA polymerase activity, assayed in vitro, which results from the treatment with cortisol. 4. Adrenalectomy causes a decrease in Mg2+-dependent RNA polymerase activity. The effect on this enzymic activity of adrenalectomy plus treatment with aflatoxin B1 is no greater than that of treatment with aflatoxin B1 alone. 5. These results suggest that the inhibition of cortisol-stimulated biochemical pathways by aflatoxin B1 is due to an inhibition of cortisol-stimulated RNA synthesis. 6. The cytoplasmic action of aflatoxin is thought to be due to a competition for receptor sites on the endoplasmic reticulum between steroid hormones and aflatoxin B1. No evidence was obtained for a similar competition for nuclear receptor sites between [3H]cortisol and aflatoxin B1. 7. No differences were observed between the activities of RNA polymerase preparations solubilized from control or aflatoxin-inhibited nuclei. 8. No differences in ‘melting’ profiles were observed between DNA and chromatin preparations isolated from control nuclei or from aflatoxin-inhibited nuclei. 9. It is suggested that aflatoxin B1 exerts its effect on RNA polymerase by decreasing the template capacity of the chromatin and that the aflatoxin ‘target’ area of the chromatin includes that region which is stimulated by cortisol. This process, however, does not involve inhibiting the movement of cortisol from the outside of the hepatic cell to the nuclear chromatin.


2008 ◽  
Vol 46 (01) ◽  
Author(s):  
F Moriconi ◽  
H Christiansen ◽  
H Christiansen ◽  
N Sheikh ◽  
J Dudas ◽  
...  

2019 ◽  
Vol 14 (1) ◽  
pp. 5-18 ◽  
Author(s):  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Roberta M. Moretti ◽  
Marina Montagnani Marelli ◽  
...  

Background: Tocotrienols (TTs) are vitamin E derivatives naturally occurring in several plants and vegetable oils. Like Tocopherols (TPs), they comprise four isoforms, α, β, γ and δ, but unlike TPs, they present an unsaturated isoprenoid chain. Recent studies indicate that TTs provide important health benefits, including neuroprotective, anti-inflammatory, anti-oxidant, cholesterol lowering and immunomodulatory effects. Moreover, they have been found to possess unique anti-cancer properties.Objective:The purpose of this review is to present an overview of the state of the art of TTs role in cancer prevention and treatment, as well as to describe recent patents proposing new methods for TTs isolation, chemical modification and use in cancer prevention and/or therapy.Methods:Recent literature and patents focusing on TTs anti-cancer applications have been identified and reviewed, with special regard to their scientific impact and novelty.Results:TTs have demonstrated significant anti-cancer activity in multiple tumor types, both in vitro and in vivo. Furthermore, they have shown synergistic effects when given in combination with standard anti-cancer agents or other anti-tumor natural compounds. Finally, new purification processes and transgenic sources have been designed in order to improve TTs production, and novel TTs formulations and synthetic derivatives have been developed to enhance their solubility and bioavailability.Conclusion:The promising anti-cancer effects shown by TTs in several preclinical studies may open new opportunities for therapeutic interventions in different tumors. Thus, clinical trials aimed at confirming TTs chemopreventive and tumor-suppressing activity, particularly in combination with standard therapies, are urgently needed.


1975 ◽  
Vol 24 (4) ◽  
pp. 517-521 ◽  
Author(s):  
Gerard J. Mulder ◽  
Arnold H.E. Pilon
Keyword(s):  

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