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M L Souto

Publications and source records attributed to M L Souto.

10 recordsLinked to original sources

Okadaic acid, useful tool for studying cellular processes.

One of the most interesting groups of substances of marine origin, from structural and pharmacological points of view are polyether toxins, which generally present a great diversity in size and potent biological activities. The subject of this review is limited to okadaic acid (OA). It was the first example of a group of polyether toxins produced by marine microalgae, which is responsible for the natural phenomena known as Diarrhetic Shellfish Poisoning, DSP red tides. These toxins are accumulated in the digestive glands of the shellfish with a disastrous effect upon the shellfish industry in many parts of the world. Thus, it has been demonstrated that OA is a highly selective inhibitor of protein phosphatases type 1 (PP1) and 2A (PP2A), subsequently that it causes dramatic increases in phosphorylation of numerous proteins as well as being a potent tumour promoter. For that reason, OA is an extremely useful tool for studying the cellular processes that are regulated by reversible phosphorylation of proteins as signal transduction, cell division and memory.

Amino Acid Sequence↗

Influence of amino acids on okadaic acid production.

Okadaic acid (OA) (1)) was the first example of a group of polyether toxins known to be produced by marine microalgae, which are responsible for the natural phenomena known as Diarrhetic Shellfish Poisoning (DSP) red tides. It is also a highly selective inhibitor of protein phosphatases type 1 (PP1) and 2A (PP2A), as well as being a potent tumour promoter. For these reasons, OA is an extremely useful tool for studying cellular processes and an important standard for polluted shellfish control. In this paper, we report on a double objective: to improve the production of toxins and verify the apparent participation of amino acids in the formation of these polyethers by monitoring their influence on the promotion of growth, total cell yield and increased in toxicity in Prorocentrum lima of the PL2V strain in batch cultures, in a modified K medium.

Amino Acids↗

Isolation and structural determination of DTX-6, a new okadaic acid derivative.

Diarrhetic shellfish poisoning is an illness caused by toxins accumulated in shellfish and produced by dinoflagellates, mainly of the Dinophysis and Prorocentrum genera. This paper reports the isolation and spectroscopic structural elucidation of a new compound, DTX-6 (2), an ester derivative of okadaic acid (OA) (1), isolated from an artificial culture of strain PLV2 of Prorocentrum lima.

Animals↗

Movement of retinal along the visual transduction path.

Movement of the ligand/receptor complex in rhodopsin (Rh) has been traced. Bleaching of diazoketo rhodopsin (DK-Rh) containing 11-cis-3-diazo-4-oxo-retinal yields batho-, lumi-, meta-I-, and meta-II-Rh intermediates corresponding to those of native Rh but at lower temperatures. Photoaffinity labeling of DK-Rh and these bleaching intermediates shows that the ionone ring cross-links to tryptophan-265 on helix F in DK-Rh and batho-Rh, and to alanine-169 on helix D in lumi-, meta-I-, and meta-II-Rh intermediates. It is likely that these movements involving a flip-over of the chromophoric ring trigger changes in cytoplasmic membrane loops resulting in heterotrimeric guanine nucleotide-binding protein (G protein) activation.

Affinity Labels↗

Growth inhibition by dehydrothyrsiferol - a non-Pgp modulator, derived from a marine red alga - in human breast cancer cell lines.

The novel marine terpenoid dehydrothyrsiferol (DHT) has been isolated from a Canarian red alga Laurencia viridis sp. nov (Ceramiales, Rhodomelaceae) (1). Its cytotoxicity against three human breast cancer cell lines, namely T47D, ZR-75-1, and Hs578T was examined and compared with the chemotherapeutic compound doxorubicin and the mitosis-inhibitor colchicine. Primary breast carcinomas exhibit MDR1 gene expression (3). As the investigated mammary cell lines did not exhibit rhodamine 123 efflux we proved in a P-glycoprotein (Pgp) overexpressing human epidermoid cancer cell line that the marine metabolite does not modulate Pgp mediated drug transport. Therefore, it could be used in Pgp expressing cancer cells without interference.

ATP Binding Cassette Transporter, Subfamily B↗

Complexation of okadaic acid: a preliminary study.

A complexation study was carried out with okadaic acid (OA) and the univalent metal ions Li+, Na+ and K+, and the divalent metal ions Ca2+ and Mg2+. K+ binding was observed identical with a complex obtained from the natural source (OAC). The pharmacological trials demonstrated that this cation has a very important influence on the pharmacological activity of okadaic acid.

Calcium↗

Evaluation of the cytotoxic activity of polyethers isolated from Laurencia.

In this paper, we report on the conformational analysis of several polyether triterpenes with a squalene carbon skeleton which exhibited significant cytotoxic activity using a Monte Carlo conformational search and spectroscopical data. These studies indicate that the conformation of the side chain C-14/C-19 and the arrangement and direction of this chain may be among the fundamental factors related to the activity of this type of metabolites.

Animals↗

Inhibitory effects of a novel marine terpenoid on sensitive and multidrug resistant KB cell lines.

Mechanisms of growth inhibition by the novel marine compound dehydrothyrsiferol (DHT) were investigated in a sensitive and an MDR+ human epidermoid cancer cell line. DHT was found to circumvent multidrug resistance mediated by P-glycoprotein. Cell cycle analysis revealed an accumulation in S-phase. The anchorage independent clonogenic growth in soft agar was not significantly reduced at IC50 concentrations. Reduced cell growth caused by induction of apoptotic or necrotic cell death could not be verified. Therefore, cell proliferation during an incubation period of five days was measured and found to be significantly reduced. We conclude that growth inhibition by dehydrothyrsiferol in KB cancer cells is not mediated by apoptosis but by growth retardation; the reasons for this are worth being investigated in detail.

ATP Binding Cassette Transporter, Subfamily B, Mem↗