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A redox-sensitive signaling pathway mediates pro-angiogenic effect of chlordecone via estrogen receptor activation

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AIM: Chlordecone is able to induce pro-angiogenic effect through an estrogen receptor (ERα) pathway involving NO release and VEGF. The present study aimed to determine the molecular mechanisms by which chlordecone promotes angiogenesis in human endothelial cells.

RESULTS: High but not low concentration of chlordecone increased mitochondrial respiratory capacity and mitochondrial DNA content in endothelial cells. The ROS scavenger MnTMPyP was able to prevent the increase of both VEGF expression and capillary length induced by chlordecone. A significant increase of cytoplasmic O production was observed after 1 and 4 h incubation of chlordecone, but not after 2 h. The NADPH oxidase inhibitor apocynin or silencing p47phox prevented angiogenesis and tube formation but also the increase in production of O at 1 h. In addition, apocynin as well silencing p47phox prevented eNOS activation and the NO synthase inhibitor L-NAME inhibited mitochondrial Oproduction. All the previous effects of chlordecone were prevented by fulvestrant.

CONCLUSION: Our results indicate that an adaptation of the mitochondrial energy metabolism occurs in the chlordecone angiogenic response. Finally, we showed that chlordecone induces endothelial cells angiogenesis by a cross-talk involving NADPH oxidase and mitochondrial Ovia a NO sensitive pathways through activation of ERα. These findings propose that a molecular mechanism may partly explain the epidemiological evidence implicating chlordecone as risk factor carcinogenesis.

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https://hal.univ-angers.fr/hal-02521224
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Soumis le : vendredi 27 mars 2020 - 12:11:55
Dernière modification le : mercredi 15 avril 2020 - 14:01:35

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Eid Alabed Alibrahim, Ramaroson Andriantsitohaina, Kévin Hardonnière, Raffaella Soleti, Sébastien Faure, et al.. A redox-sensitive signaling pathway mediates pro-angiogenic effect of chlordecone via estrogen receptor activation. International journal of biochemistry & cell biology, 2018, 97, pp.83-97. ⟨10.1016/j.biocel.2018.02.008⟩. ⟨hal-02521224⟩

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