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Biomedical subjects

A Fellous

Publications and source records attributed to A Fellous.

46 records · Page 3Linked to original sources
PubMed1979

Competitive inhibition of colchicine binding to tubulin by microtubule-associated proteins.

Microtubule-associated proteins (MAPs) promote tubulin polymerization, whereas colchicine inhibits this process. In this paper, MAPs have been shown to inhibit colchicine binding to tubulin in a competitive manner. Attempts were made to identify which of the MAPs fraction(s) was responsible; both tau protein (a thermostable molecule with a molecular weight of approximately 70,000) and a high molecular weight fraction (HMW) were able to compete with colchicine. In contrast, Mg2+, which also induces microtubule assembly in vitro, had no effect on colchicine binding to tubulin.

Animals↗
PubMed1979

Thyroid hormones and neurotubule assembly in vitro during brain development.

A new model has been used to evaluate the effects of thyroid hormones on brain development. This model is based on the assumption that the major effect of thyroid hormones is in regulating the rate of neurite growth of the rat brain at early stages of postnatal development. Microtubules were chosen as markers of neurite growth. We tested, therefore, whether the rate of microtubule assembly in vitro is under thyroid hormone control. The following results were obtained: The rate of tubulin assembly into microtubules in vitro seems to be thyroid hormone dependent: (a) in 15-day-old hypothyroid rats the rates of tubulin assembly in vitro are low, comparable to those levels found in normal rats on day 3; (b) normal rates of assembly in vitro are restored upon addition of very small amounts of microtubule fragments which act as nucleating centers in the process of microtubule formation; (c) addition of microtubule-associated proteins to a hypothyroid preparation restores maximal assembly rates; similar results were obtained on adding one of the microtubule-associated proteins (purified tau protein); (d) physiological amounts of thyroid hormones completely restore normal assembly rates provided that they are administered very early after birth; (e) the ability of tubulin to assemble maximally does not seem to be permanently impaired, since normal assembly rates are spontaneously restored when hypothyroidism is maintained until an adult stage; (f) normal microtubule assembly is observed when hypothyroidism is produced at an adult stage. The model which may be constructed from these results implies that thyroid hormones are required briefly after birth to accelerate the rate of microtubule assembly thus allowing intensive neurite growth during the critical period of brain development.

Aging↗
PubMed1977

Microtubule assembly in vitro. Purification of assembly-promoting factors.

The role of microtubule-associated proteins in the assembly of tubulin to microtubules in vitro has been studied. 1. It has been confirmed that pure tubulin obtained by phosphocellulose column chromatography does not significantly assemble in vitro in the absence of minor components which co-polymerize with tubulin. Although tubulin aggregates in a morpholino-ethanesulfonate buffer containing high Mg2+ concentrations, this process was neither inhibited by Ca2+ or colchicine, nor reversed by cold exposure. 2. Microtubule-associated proteins were prepared, either by phosphocellulose column chromatography or by a direct method based on boiling reassembled microtubules in the presence of 2 mM dithiothreitol and 0.75 M NaCl. From each of these preparations two protein fractions were purified, either by Ultrogel ACA34 chromatography or by sucrose gradient ultracentrifugation. The first one, with a high molecular weight, did not promote tubulin assembly; ageing of this material did not induce any activity. On the other hand, the second fraction, with an apparent molecular weight of 70 000 (tau protein), when almost completely purified, was active in promoting assembly. Thus a single specific protein is able to promote assembly of pure tubulin.

Animals↗
PubMedDate not supplied

Taxol resistance.

BACKGROUND: Taxol has gained considerable attention in cancer therapy in recent years and is successfully used in treating a variety of tumors, including those of the breast, ovary and lung. Despite its preclinical and clinical success, the ability of tumors to develop an acquired resistance to drugs used for treatment remains a major obstacle to cancer cure. A better understanding of the various mechanisms of Taxol resistance may have important implications for strategies designed for cancer treatment. METHOD: This review summarizes the information available to date concerning the effects of Taxol and the development of drug resistance, focusing particularly on alterations in microtubules. RESULTS AND DISCUSSION: Acquired resistance to Taxol is a function of multiple adaptations. Although the cellular transport of Taxol appears to be an important mechanism of resistance to Taxol, altered transcription and posttranslational modification of microtubular changes may be involved in the mechanism of drug resistance.

Antineoplastic Agents, Phytogenic↗