Selective inactivation of rabbit reticulocyte initiation factor eIF-3 by helenalin

Williams, W.L.; Chaney, Stephen G.; Willingham, Walker; Considine, R. Tobias; Hall, Iris H.; Lee, Kuo Hsiung̀

doi:10.1016/0167-4781(83)90072-6

Cited by 9 publications

(16 citation statements)

References 28 publications

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“…Rabbit reticulocyte lysates were prepared as described previously (Williams et al, 1983). New Zealand Minikin rabbits weighing 1-2 kg were used.…”

Section: Methodsmentioning

confidence: 99%

“…Isolation of "runoff" ribosomes (Schreier & Staehelin, 1973), 40S subunits (Schreier & Staehelin, 1973), and pH 5 enzymes (Kruh, 1968) from rabbit reticulocytes were prepared essentially as described previously except that the final storage buffer for the 40S subunits contained only 100 mM dithiothreitol and the final storage buffer for runoff ribosomes and pH 5 enzymes contained no added thiol compound. The reticulocyte initiation factor preparations used in these experiments were prepared as described by Williams et al (1983).…”

Section: Methodsmentioning

confidence: 99%

“…The mechanism of protein synthesis inhibition by helenalin has been studied in some detail. Helenalin specifically inhibits at the level of initiation in both P-388 (Liou et al, 1983) and rabbit reticulocyte (Williams et al, 1983) systems. With use of fractionated systems, it appears likely that eIF-3 is the only initiation factor directly sensitive to inactivation by helenalin (Liou et al, 1983;Williams et al, 1983).…”

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confidence: 99%

“…Helenalin specifically inhibits at the level of initiation in both P-388 (Liou et al, 1983) and rabbit reticulocyte (Williams et al, 1983) systems. With use of fractionated systems, it appears likely that eIF-3 is the only initiation factor directly sensitive to inactivation by helenalin (Liou et al, 1983;Williams et al, 1983). Thus, helenalin appears to possess a remarkable degree of selectivity as a sulfhydryl reagent.…”

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confidence: 99%

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Indirect inactivation of rabbit reticulocyte initiation factor eIF-2 by helenalin and bis(helenalinyl) malonate

Williams¹,

Chaney²,

Hall³

et al. 1984

Biochemistry

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Helenalin and bis(helenalinyl) malonate, sesquiterpene lactones that react primarily with exposed sulfhydryl groups, were shown to be equally effective inhibitors of endogenous protein synthesis in rabbit reticulocyte lysates. By use of partially fractionated systems, it was possible to show that helenalin preferentially inhibited the conversion of the ternary initiation complex to the 48S preinitiation complex. Previous experiments have shown that this preferential inhibition is due to selective inactivation of eIF-3 [Williams, W. L., Chaney, S. G., Willingham, W., Considine, R. T., Hall, I. H., & Lee, K.-H. (1983) Biochim. Biophys. Acta 740, 152-162]. Bis(helenalinyl) malonate was much less active as an inhibitor of 48S complex formation than helenalin and clearly did not possess sufficient activity in that assay to explain its effectiveness as a protein synthesis inhibitor in whole lysates. Kinetic studies also showed a clear difference between the mechanism of action of these two drugs. Bis(helenalinyl) malonate inactivated protein synthesis in reticulocyte lysates only after a lag of 10 min, and the inhibition of protein synthesis could be completely reversed by the addition of 5 mM cAMP. Helenalin showed more complex kinetics. While full inhibition only occurred after a lag of 10-15 min, a partial inhibition was observed from very early times. cAMP at 5 mM was only partially able to reverse inhibition by helenalin. Phosphorylation studies showed that both helenalin and bis(helenalinyl) malonate were equally effective at activating eIF-2 alpha kinase and indirectly causing phosphorylation of eIF-2.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Rabbit reticulocyte lysates were prepared as described previously (Williams et al, 1983). New Zealand Minikin rabbits weighing 1-2 kg were used.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Indirect inactivation of rabbit reticulocyte initiation factor eIF-2 by helenalin and bis(helenalinyl) malonate

Williams¹,

Chaney²,

Hall³

et al. 1984

Biochemistry

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“…The main modes of action are the inhibition of DNA, RNA and protein synthesis. Among others, the specific metabolic targets are the thiol-bearing enzymes IMP dehydrogenase, DNA polymerase a, ribonucleoside reductase (33,36,38), elF-2 kinase, and the elongation factor eIF-3 (29,30). Furthermore, the compounds lower the cellular glutathione level (39,40).…”

Section: Biological Activities Of Arnica Sesquiterpene Lactonesmentioning

confidence: 99%

Arnica Flowers: Pharmacology, Toxicolgy, and Analysis of the Sesquiterpene Lactones—Their Main Active Substances

Willuhn

1998

ACS Symposium Series

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Arnica flowers from the European Compositae Arnica montana have been used in traditional medicine to treat a large variety of different ailments. It has been shown that the known diverse effects of the flowers correlate closely with the pharmacological and toxicological profile of their constituents helenalin, 11α,13-dihydrohelenalin and their esters, which therefore must be considered as their main active compounds. Methods for their qualitative and quantitative determination have been established and the variability in flowers from different geographical origin investigated. Arnica chamissonis ssp. foliosa is used as alternative source for the official "Arnicae flos." In addition to the sesquiterpene lactones of A. montana, they contain 2,3-dihydro-2α-hydroxy-and 2,3-dihydro-2α-,4α-dihydroxy-helenanolide derivatives. The qualitative and quantitative variation is much larger than in the case of A. montana flowers, but populations exist equal to that of A. montana.Arnica flowers from the European Arnica montana L. have been extensively used in traditional medicine to treat a large variety of different ailments. First written records exist from the 16th century when Arnica flowers were used externally and internally in injuries and accidents such as sprains, dislocations, haematomas and oedema associated with fractures. Many vernacular names for this medicinal plant from that time, such as "fall herb", "break herb" or "wound herb" point to this indication. In the following centuries the range of indications for Arnica flowers was enlarged to include treatment of heart and circulatory diseases, chronical diseases such as asthma and rheumatic pains, feverish conditions, menstruation complaints and many other diseases. The plant was named "Panacea lapsorum" after the hypothetical medicine "Panazee," of which the ancient physicians were always dreaming. This imagined 118

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Antitumor Agents 68: Effects of a Series of Helenalin Derivatives on P-388 Lymphocytic Leukemia Nucleic Acid and Protein Synthesis

Hall

Williams

Chaney

et al. 1985

Journal of Pharmaceutical Sciences

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Selective inactivation of rabbit reticulocyte initiation factor eIF-3 by helenalin

Cited by 9 publications

References 28 publications

Indirect inactivation of rabbit reticulocyte initiation factor eIF-2 by helenalin and bis(helenalinyl) malonate

Indirect inactivation of rabbit reticulocyte initiation factor eIF-2 by helenalin and bis(helenalinyl) malonate

Arnica Flowers: Pharmacology, Toxicolgy, and Analysis of the Sesquiterpene Lactones—Their Main Active Substances

Antitumor Agents 68: Effects of a Series of Helenalin Derivatives on P-388 Lymphocytic Leukemia Nucleic Acid and Protein Synthesis

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