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G-quadruplexes Sequester Free Heme in Living Cells

G-quadruplexes Sequester Free Heme in Living Cells

Lucas T Gray, Emilia Puig Lombardi, Daniela Verga, Alain Nicolas, Marie-Paule Teulade-Fichou, Arturo Londoño-Vallejo, Nancy Maizels

Cell Chem Biol. 2019 Dec 19;26(12):1681-1691.e5.

PMID: 31668518

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP929895454	PhenDC3		929895-45-4	Price

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