�ber die Trennung und Mitosewirkung der Lumicolchicine

Linskens, H. F.; Wulf, Wilhelm

doi:10.1007/bf00628998

Cited by 14 publications

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“…To separate the colchicine-removal step from subsequent polymerization, ultraviolet light (UV) irradiation was used (12,13). Colchicine, when irradiated with long-wave ultraviolet light, is photochemically converted to lumi-colchicine (11,18); lumi-colchicine has no measureable affinity for microtubule subunits (19). Therefore, reversal of colchicine inhibition was examined by preparation of subunits complexed with colchicine and then irradiation of the subunit-colchicine complex with UV; the lumi-colchicine produced dissociated rapidly from the subunits.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Aggregation of Cytoplasmic Microtubule Subunits

Borisy

Olmsted

Klugman

1972

Proc. Natl. Acad. Sci. U.S.A.

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The colchicine-binding protein in porcinebrain tissue is a dimer of molecular weight 110,000 that is believed to be the subunit of neuronal microtubules. Conditions are established under which the dimers aggregate with reproducible kinetics. This aggregation reaction, which is monitored by development of turbidity, has the following characteristics: (a) Colchicine inhibits development of turbidity; (b) the reaction inhibited by colchicine is reversed by long-wave ultraviolet irradiation; (c) the aggregation is temperature-dependent; (d) the reaction is nucleotide triphosphate-specific, being stimulated by 1 mM GTP; (e) the reaction appears to be specific for microtubule subunits since in the presence of other added proteins and in crude cell extracts, only microtubule subunits aggregate. On the basis of these criteria, we conclude that we have established an in vitro system for the aggregation of microtubule subunits that shares some of the properties characteristic of the in vivo assembly of cytoplasmic and spindle microtubules.

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Section: Resultsmentioning

confidence: 99%

In Vitro Aggregation of Cytoplasmic Microtubule Subunits

Borisy

Olmsted

Klugman

1972

Proc. Natl. Acad. Sci. U.S.A.

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Photoisomerization of colchicine. Loss of significant antimitotic activity in human lymphocytes

Sagorin

Ertel

1972

Arthritis & Rheumatism

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Colchicine exposed to ultraviolet light is photoisomerized to form the lumicolchicines. Other studies have shown that light-altered colchicine has reduced biologic activity in plants and lower animals. The effects of colchicine and lumicolchicine on arresting mitosis in metaphase were studied in human lymphocytes in tissue culture. Lumicolchicine was ineffective and not different from controls, even in concentrations of 1 x loa M. The possible clinical relevance of these data are discussed.Colchicine and certain related alkaloids are highly light-sensitive. When colchicine in solution is exposed to sunlight for prolonged periods of time or to ultraviolet light for shorter times, three products, a-, /3-, and y-lumicolchicine, are isolated in varying quantities, depending upon the experimental conditions (1). These photoisomers can be differentiated from the parent compound and each other by such physical properties as solubility in alcohol, melting point and ultraviolet spectra. One feature they share is the absence of the 350 m p absorption band associated with the troponoid system of colchicine (2). Their structural formulae (Fig 1) have been established recently with some certainty; 8-and y-lumicolchicine a r e stereoisomers (3) and a-lumicolchicine is a dimer of /34umicolchicine (2).Previous work from this laboratory (4) has shown that when a dilute nonaqueous solution of '4c-or unlabeled colchicine was exposed to ultraviolet light for 1 to 7 days and purified by thin-layer and paper chromatography, a single new radioactive peak or untraviolet absorbing spot was quantitatively formed. T h e new substance, which migrated faster than colchicine in all chromatographic systems tested, is undoubtedly one or more of the lumicolchicines as evidenced by the disappearance of the 350 mfi absorption band.Colchicine is clinically beneficial in the treatment of acute gout. It has, in addition, a number of biologic actions, even in small concentration. Colchicine specifically binds to proteins in the cellular organoids termed microtubules (5). Such binding results in disruption of the microtubular structure into its subunits, leading to mitotic arrest in metaphase (6). The purpose of this paper is to report on the effect of

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Colchicine: A State‐of‐the‐Art Review

Levy,

Spino,

Read

1991

Pharmacotherapy

129

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Colchicine is an ancient drug that is attracting renewed interest because of its actions at a subcellular level. Specifically, it interferes with microtubule growth and therefore affects mitosis and other microtubule‐dependent functions. Various mechanisms have been proposed to account for the action of colchicine in acute gouty arthritis, its interaction with cellular membrane and cyclic 3′,5′‐adenosine monophosphate, and its action in amyloidosis. Pharmacokinetic studies have been relatively limited and their results somewhat contradictory, with mean terminal elimination half‐lives of 19 minutes to 9 hours being reported. Some of these differences may be attributed to assay difficulties. Colchicine can cause gastrointestinal side effects and should be used with care to protect patients from toxic doses. Colchicine‐induced myopathy and neuropathy may be more frequent than previously recognized, and therefore patients receiving long‐term therapy should be monitored carefully. Bone marrow depression has been reported, primarily in cases of acute colchicine intoxication, and intravenous administration of the drug has been associated with severe pancytopenia and death. Colchicine intoxication causes multiple organ failure. Because of its cytogenic effects and reported association with Down's syndrome, the agent should not be used by pregnant women.

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�ber die Trennung und Mitosewirkung der Lumicolchicine

Cited by 14 publications

References 1 publication

In Vitro Aggregation of Cytoplasmic Microtubule Subunits

In Vitro Aggregation of Cytoplasmic Microtubule Subunits

Photoisomerization of colchicine. Loss of significant antimitotic activity in human lymphocytes

Colchicine: A State‐of‐the‐Art Review

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