2023-09-14 カロリンスカ研究所(KI)
◆これにより、NO-ferrohemeは実際に血管を拡張し、信号伝達カスケードを活性化することが確認されました。今後の課題は、内皮細胞で生成される内因性のNO-ferrohemeが本当に信号物質であることを確認し、その体内での合成メカニズムを詳細に理解することです。
<関連情報>
- https://news.ki.se/researchers-present-novel-principle-for-nitric-oxide-mediated-signalling-in-blood-vessels
- https://www.nature.com/articles/s41589-023-01411-5
NO-フェロヘムは血管系におけるシグナル伝達体である NO-ferroheme is a signaling entity in the vasculature
Andrei L. Kleschyov,Zhengbing Zhuge,Tomas A. Schiffer,Drielle D. Guimarães,Gensheng Zhang,Marcelo F. Montenegro,Angela Tesse,Eddie Weitzberg,Mattias Carlström & Jon O. Lundberg
Nature Chemical Biology Published:14 September 2023
DOI:https://doi.org/10.1038/s41589-023-01411-5
Abstract
Despite wide appreciation of the biological role of nitric oxide (NO) synthase (NOS) signaling, questions remain about the chemical nature of NOS-derived bioactivity. Here we show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species, which can transfer between proteins, partition into a hydrophobic phase and directly activate the sGC–cGMP–PKG pathway without intermediacy of free NO. The NO-ferroheme species (with or without a protein carrier) efficiently relax isolated blood vessels and induce hypotension in rodents, which is greatly potentiated after the blockade of NOS activity. While free NO-induced relaxations are abolished by an NO scavenger and in the presence of red blood cells or blood plasma, a model compound, NO-ferroheme-myoglobin preserves its vasoactivity suggesting the physiological relevance of NO-ferroheme species. We conclude that NO-ferroheme behaves as a signaling entity in the vasculature.
