G-quadruplexes Sequester Free Heme in Living Cells.

Autor:	Gray LT; Department of Immunology, University of Washington, 1959 NE Pacific St., Seattle, WA 98195, USA., Puig Lombardi E; Institut Curie, Centre de Recherche, CNRS-UMR3244, PSL Research University, Paris 75005, France., Verga D; Institut Curie, Centre de Recherche, CNRS-UMR9187, INSERM-U1196, PSL Research University, Sorbonne Universités, Orsay 91405, France; CNRS UMR9187, INSERM U1196, Université Paris Sud, Université Paris-Saclay, Orsay 91405, France., Nicolas A; Institut Curie, Centre de Recherche, CNRS-UMR3244, PSL Research University, Paris 75005, France., Teulade-Fichou MP; Institut Curie, Centre de Recherche, CNRS-UMR9187, INSERM-U1196, PSL Research University, Sorbonne Universités, Orsay 91405, France; CNRS UMR9187, INSERM U1196, Université Paris Sud, Université Paris-Saclay, Orsay 91405, France., Londoño-Vallejo A; Institut Curie, Centre de Recherche, CNRS-UMR3244, PSL Research University, Paris 75005, France., Maizels N; Department of Immunology, University of Washington, 1959 NE Pacific St., Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, 1959 NE Pacific St., Seattle, WA 98195, USA. Electronic address: maizels@u.washington.edu.
Jazyk:	angličtina
Zdroj:	Cell chemical biology [Cell Chem Biol] 2019 Dec 19; Vol. 26 (12), pp. 1681-1691.e5. Date of Electronic Publication: 2019 Oct 23.
DOI:	10.1016/j.chembiol.2019.10.003
Abstrakt:	Heme is an essential cofactor for many enzymes, but free heme is toxic and its levels are tightly regulated. G-quadruplexes bind heme avidly in vitro, raising the possibility that they may sequester heme in vivo. If so, then treatment that displaces heme from quadruplexes is predicted to induce expression of genes involved in iron and heme homeostasis. Here we show that PhenDC3, a G-quadruplex ligand structurally unrelated to heme, displaces quadruplex-bound heme in vitro and alters transcription in cultured human cells, upregulating genes that support heme degradation and iron homeostasis, and most strikingly causing a 30-fold induction of heme oxidase 1, the key enzyme in heme degradation. We propose that G-quadruplexes sequester heme to protect cells from the pathophysiological consequences of free heme. (Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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