Abstract：
:The biotoxin okadaic acid (OA) is a lipophilic secondary metabolite of marine microalgae. Therefore, OA accumulates in the fatty tissue of various shellfish and may thus enter the food chain. The ingestion of OA via contaminated marine species can lead to the diarrhetic shellfish poisoning syndrome characterized by the occurrence of a series of acute gastrointestinal symptoms in humans. In addition, genotoxicity and tumor-promoting properties of OA might constitute a long-term threat to human health. In order to deepen our understanding of the molecular effects of OA, we compared long-term (14 d) and short-term (24 h and 48 h) apoptotic effects of the compound on human HepaRG hepatocarcinoma cells. Cells were treated either with single doses for 24 and 48 h, respectively, or seven times over a period of 14 d, so that the cumulated quantities of OA in the long-term approach were equal to the single doses upon short-term treatment. Both short-term treatment scenarios led to the induction of apoptosis. Specific caspase activation assays and transcriptional analysis of mRNAs encoding proteins involved in the regulation of apoptosis suggest that OA-induced apoptosis occurs presumably by activation of the intrinsic apoptotic pathway. In contrast, effects were much less pronounced in case of long-term treatment. This is possibly linked to cellular protective mechanisms against low amounts of toxins, e.g. transporter-mediated efflux. In conclusion, our results show a clear concentration- and time-dependency of OA-mediated apoptotic effects in HepaRG cells and contribute to the elucidation of molecular effects of OA.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Dietrich J,Schindler M,Lampen A,Braeuning A,Hessel-Pras Sdoi
10.1016/j.cbi.2020.108937subject
Has Abstractpub_date
2020-02-01 00:00:00pages
108937eissn
0009-2797issn
1872-7786pii
S0009-2797(19)31357-2journal_volume
317pub_type
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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