Evidence map›Paper›PMID 28584062›Full record

ArticleCirculation research2017

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

Mizanur M Rahaman, Anh T Nguyen, Megan P Miller, Scott A Hahn, Courtney Sparacino-Watkins, Soma Jobbagy, Nolan T Carew, Nadiezhda Cantu-Medellin, Katherine C Wood, Catherine J Baty and 5 more

Open access · bronzeAbstract read
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In one paragraph

Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 89 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Mizanur M RahamanFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Anh T NguyenFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Megan P MillerFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Scott A HahnFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Courtney Sparacino-WatkinsFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Soma JobbagyFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Nolan T CarewFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Nadiezhda Cantu-MedellinFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Katherine C WoodFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Catherine J BatyFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Francisco J SchopferFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Eric E KelleyFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Mark T GladwinFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Emil MartinFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.).
Adam C StraubFrom the Heart, Lung, Blood and Vascular Medicine Institute (M.M.R., A.T.N., M.P.M., S.A.H., C.S.-W., N.T.C., N.C.-M., K.C.W., M.T.G., A.C.S.), Division of Pulmonary, Allergy and Critical Care Medicine (C.S.-W., M.T.G.), Department of Pharmacology and Chemical Biology (S.J., C.J.B., F.J.S., A.C.S.), and Division of Renal-Electrolyte (C.J.B.), University of Pittsburgh, PA; Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown (E.E.K.); and Department of Internal Medicine, Division of Cardiology, University of Texas Houston Medical School (E.M.). astraub@pitt.edu.
West Virginia University · US

Funding

Renal and Epithelial Biology Training ProgramT32DK061296 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2002 to 2022
$3.1M
Novel role of smooth muscle B5 reductase in Sickle Cell DiseaseR01HL133864 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STRAUB, ADAM CARL · 2016 to 2019
$2.4M
Vascular Smooth Muscle and Blood Pressure Regulation By Cyb5R3²R01HL128304 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STRAUB, ADAM CARL · 2016 to 2020
$2.4M
Protective effects of nitro-oleic acid in hypertensive chronic kidney injuryF30DK108391 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOBBAGY, SOMA · 2015 to 2018
$195k
NHLBI NIH HHS R01 HL128304NHLBI NIH HHS R01 HL133864NIDDK NIH HHS F30 DK108391NIDDK NIH HHS T32 DK061296
6 · The paper itself

Abstract

rationaleSoluble guanylate cyclase (sGC) heme iron, in its oxidized state (Fe

objectiveAlthough 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

resultsOxidant 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 smooth muscle cells reveal that cytochrome b5 reductase 3 expression and activity is critical for NO-stimulated cGMP production and vasodilation. Mechanistically, we show that cytochrome b5 reductase 3 directly reduces oxidized sGC required for NO sensitization as assessed by biochemical, cellular, and ex vivo assays.

conclusionsTogether, these findings identify new insights into NO-sGC-cGMP signaling and reveal cytochrome b5 reductase 3 as the first identified physiological sGC heme iron reductase in vascular smooth muscle cells, serving as a critical regulator of cGMP production and protein kinase G-dependent signaling.

Indexed as

AnimalsAortaBenzoatesCells, CulturedCyclic GMPCytochrome-B(5) ReductaseDose-Response Relationship, DrugMiceMice, Inbred C57BLMuscle, Smooth, VascularOxidation-ReductionRatsSignal TransductionSoluble Guanylyl CyclaseVasodilationBAY 58-2667BenzoatesCyb5R3 protein, ratCyclic GMPCytochrome-B(5) ReductaseSoluble Guanylyl Cyclaseguanosinehemeironnitric oxidereactive oxygen species

Identifiers

PMID28584062
PMCPMC5527687
OpenAlexW2623267848

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.