Year: 2023
Type: article
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.
Source: Nature Chemical Biology
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
Awards: Therapeutic implications of bioactive nitrogen oxides in the triad of reno-cardio-metabolic disorders, Targeting Renal Microvascular Oxidative Stress in Cardiovascular & Metabolic Disease, G3743207060, G5490416564, Increasing NO Bioavailability in Cardiovascular and Metabolic Disease, G5840233480, G6550989385, The nitrate-nitrite-nitric oxide pathway in critical illness
OpenAlex ID: W4386741086