Cytochrome b5 Reductase 3 Modulates Soluble Guanylate Cyclase Redox State and cGMP Signaling.

ABSTRACT:

Rationale

Soluble guanylate cyclase (sGC) heme iron, in its oxidized state (Fe³⁺), is desensitized to NO and limits cGMP production needed for downstream activation of protein kinase G-dependent signaling and blood vessel dilation.

Objective

Although reactive oxygen species are known to oxidize the sGC heme iron, the basic mechanism(s) governing sGC heme iron recycling to its NO-sensitive, reduced state remain poorly understood.

Methods and results

Oxidant challenge studies show that vascular smooth muscle cells have an intrinsic ability to reduce oxidized sGC heme iron and form protein-protein complexes between cytochrome b5 reductase 3, also known as methemoglobin reductase, and oxidized sGC. Genetic knockdown and pharmacological inhibition in vascular sm

SUBMITTER: Rahaman MM 

PROVIDER: S-EPMC5527687 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature