Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development Journal Article

   

Authors:	Tschuck, J.; Padmanabhan Nair, V.; Galhoz, A.; Zaratiegui, C.; Tai, H. M.; Ciceri, G.; Rothenaigner, I.; Tchieu, J.; Stockwell, B. R.; Studer, L.; Cabianca, D. S.; Menden, M. P.; Vincendeau, M.; Hadian, K.
Article Title:	Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development
Abstract:	The development of functional neurons is a complex orchestration of multiple signaling pathways controlling cell proliferation and differentiation. Because the balance of antioxidants is important for neuronal survival and development, we hypothesized that ferroptosis must be suppressed to gain neurons. We find that removal of antioxidants diminishes neuronal development and laminar organization of cortical organoids, which is fully restored when ferroptosis is inhibited by ferrostatin-1 or when neuronal differentiation occurs in the presence of vitamin A. Furthermore, iron-overload-induced developmental growth defects in C. elegans are ameliorated by vitamin E and A. We determine that all-trans retinoic acid activates the Retinoic Acid Receptor, which orchestrates the expression of anti-ferroptotic genes. In contrast, retinal and retinol show radical-trapping antioxidant activity. Together, our study reveals an unexpected function of vitamin A in coordinating the expression of essential cellular gatekeepers of ferroptosis, and demonstrates that suppression of ferroptosis by radical-trapping antioxidants or by vitamin A is required to obtain mature neurons and proper laminar organization in cortical organoids. © The Author(s) 2024.
Keywords:	signal transduction; survival; controlled study; human cell; genetics; flow cytometry; cell proliferation; mouse; animal; cytology; metabolism; animals; mice; gene expression; signaling; fluorescence; clinical protocol; cell differentiation; neurons; drug effect; cell culture; western blotting; antioxidant; antioxidants; alpha tocopherol; antioxidant activity; caenorhabditis elegans; retinol; nerve cell differentiation; nervous system development; neurogenesis; nerve cell; lipid peroxidation; lipid metabolism; retinoic acid; polyacrylamide gel electrophoresis; nervous system; cell; vitamin a; retinoic acid receptor; vitamin e; caenorhabditis elegans protein; caenorhabditis elegans proteins; rna isolation; brain cell; tretinoin; iron overload; receptors, retinoic acid; genetic differentiation; protein denaturation; ferroptosis; humans; human; article; biological processes; cell viability assay; organoids; organoid; ht-1080 cell line; cortical organoid; cyclohexylamines; phenylenediamines; chondroitin sulfate iron; cyclohexylamine derivative; ferrostatin-1; phenylenediamine derivative
Journal Title:	Nature Communications
Volume:	15
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2024-09-01
Start Page:	7611
Language:	English
DOI:	10.1038/s41467-024-51996-1
PUBMED:	39218970
PROVIDER:	scopus
PMCID:	PMC11366759
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85202851177&doi=10.1038%2fs41467-024-51996-1&partnerID=40&md5=aa8fa3366409c9927bfc793d90a7331a
Notes:	Article -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/219202