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

Abstract

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 O2- 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 O2- at 1 h. In addition, apocynin as well silencing p47phox prevented eNOS activation and the NO synthase inhibitor L-NAME inhibited mitochondrial O2-production. 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 O2-via 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.

• Authors: Eid Alabed Alibrahim, Ramaroson Andriantsitohaina, Kévin Hardonnière, Raffaella Soleti, Sébastien Faure, Gilles Simard
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 97 Pg. 83-97 (04 2018) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 29452237 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• ESR1 protein, human
• Estrogen Receptor alpha
• Chlordecone

Topics

• Apoptosis (drug effects)
• Chlordecone (toxicity)
• Energy Metabolism (drug effects)
• Estrogen Receptor alpha (metabolism)
• Human Umbilical Vein Endothelial Cells (metabolism, pathology)
• Humans
• Male
• Mitochondria (metabolism, pathology)
• Neovascularization, Pathologic (chemically induced, metabolism, pathology)
• Signal Transduction (drug effects)