This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Matias, W G Articles by Creppy, E E Search for Related Content PubMed PubMed Citation Articles by Matias, W G Articles by Creppy, E E Social Bookmarking                         What's this?

Oxygen reactive radicals production in cell culture by okadaic acid and their implication in protein synthesis inhibition

A Traore

M Bonini

Laboratory of Toxicology and Applied Hygiene, Faculty of Pharmaceutical Sciences, University Victor Segalen Bordeaux 2, 146 Rue Léo-Saignat, F33076 Bordeaux, France

A Sanni

Faculty of Sciences and Technology, Cotonou, Bénin

E E Creppy

Laboratory of Toxicology and Applied Hygiene, Faculty of Pharmaceutical Sciences, University Victor Segalen Bordeaux 2, 146 Rue Léo-Saignat, F33076 Bordeaux, France

Okadaic acid (OA), a diarrhetic shellfish toxin is a potent promoter of tumours in mouse skin and a specific inhibitor of protein phosphatases 1 and 2A. Recently it has been shown that OA inhibited protein synthesis in a cell-free system, with 50% inhibitory concentration of 6.3610^{7 12} M but the mechanism whereby this inhibition is mediated was still unclear. In the present study, the effect of OA on protein synthesis in Vero cell cultures was investigated. Protein synthesis was inhibited by OA alone in Vero cells in a concentration-dependent manner (IC₅₀=27 ng/ml i.e. 3.3610^{7 8} M). Since OA also induced lipid peroxidation and likely oxygen reactive radicals, it was interesting to know whether these radicals impair the protein synthesis process. Therefore, SOD+catalase known as scavenger of active oxygen radicals were added in the culture medium in the presence of OA and labelled leucine. These enzymes partially prevented the inhibition of protein synthesis induced by OA, indicating that the formation of high reactive oxygen free radicals could be one of the pathways this marine toxin induces its toxicity. Since the prevention by SOD+catalase was only partial (the IC₅₀ increased from 27 ng/ml to 48 ng/ml i.e. 3.3610^{7 8} M to 5.9610^{7 8} M)itwas speculated that the production of oxygen reactive radical scavengered by SOD+catalase is not the main mechanism whereby OA induces its cytotoxicity. Vitamins E and C completely prevent the lipid peroxidation induced by OA in cells, but failed to reduce the inhibition of protein synthesis to the same level, indicating that a more specific mechanism might be responsible for protein synthesis inhibition. That is the hyperphosphorylation of elongation factor EF-2 in the protein synthesis machinery. However our results pointed to lipid peroxidation being a precocious phenomenon following the OA exposure, since a concentrationwithenhancedMDAproductionwaslower than that inducing significant cellular protein synthesis inhibition.

Key Words: okadaic acid • Vero cells • protein synthesis inhibition • SOD+catalase • prevention • vitamins E and C

Human & Experimental Toxicology, Vol. 18, No. 10, 634-639 (1999)
DOI: 10.1191/096032799678839473


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. E. Reilly, V. B. Patel, T. J. Peters, and V. R. Preedy In Vivo Rates of Skeletal Muscle Protein Synthesis in Rats Are Decreased by Acute Ethanol Treatment but Are Not Ameliorated by Supplemental {{alpha}}-Tocopherol J. Nutr., December 1, 2000; 130(12): 3045 - 3049. [Abstract] [Full Text] [PDF]