Evidence map›Paper›PMID 21741353›Full record

ArticleArchives of biochemistry and biophysics2011

Mutations of human cytochrome P450 reductase differentially modulate heme oxygenase-1 activity and oligomerization.

Christopher C Marohnic, Warren J Huber Iii, J Patrick Connick, James R Reed, Karen McCammon, Satya P Panda, Pavel Martásek, Wayne L Backes, Bettie Sue S Masters

Abstract read
In one paragraph

Article in Archives of biochemistry and biophysics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

16 citing papers in PubMed, 22 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

9 authors at 3 institutions in 2 countries.

Christopher C MarohnicThe University of Texas Health Science Center at San Antonio, Department of Biochemistry, USA. masters@uthscsa.edu
Warren J Huber Iii
J Patrick Connick
James R Reed
Karen McCammon
Satya P Panda
Pavel Martásek
Wayne L Backes
Bettie Sue S Masters
Louisiana State University Health Sciences Center New Orleans · USThe University of Texas Health Science Center at San Antonio · USCharles University · CZ

Funding

Role of microbiota in increased influenza severity due to particulate matter exposureP42ES013648 · NIEHS · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI NOEL, ALEXANDRA · 2009 to 2024
$27.6M
Molecular & Cellular Effects of Human Mutations in Cytochrome P450 ReductaseR01GM081568 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI ROMAN, LINDA J · 2008 to 2016
$4.5M
TOXICOLOGICAL SIGNIFICANCE OF ALKYLBENZENE METABOLISMR01ES004344 · NIEHS · LSU HEALTH SCIENCES CENTER · PI BACKES, WAYNE L · 1996 to 2013
$4.0M
TOXICOLOGICAL SIGNIFICANCE OF ALKYLBENZENE METABOLISMR29ES004344 · NIEHS · LOUISIANA STATE UNIV HSC NEW ORLEANS · PI BACKES, WAYNE L · 1988 to 1992
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NIEHS NIH HHS ES004344NIEHS NIH HHS P42 ES013648NIEHS NIH HHS R01 ES004344NIGMS NIH HHS GM081568NIGMS NIH HHS R01 GM081568
6 · The paper itself

Abstract

Genetic variations in POR, encoding NADPH-cytochrome P450 oxidoreductase (CYPOR), can diminish the function of numerous cytochromes P450, and also have the potential to block degradation of heme by heme oxygenase-1 (HO-1). Purified full-length human CYPOR, HO-1, and biliverdin reductase were reconstituted in lipid vesicles and assayed for NADPH-dependent conversion of heme to bilirubin. Naturally-occurring human CYPOR variants queried were: WT, A115V, Y181D, P228L, M263V, A287P, R457H, Y459H, and V492E. All CYPOR variants exhibited decreased bilirubin production relative to WT, with a lower apparent affinity of the CYPOR-HO-1 complex than WT. Addition of FMN or FAD partially restored the activities of Y181D, Y459H, and V492E. When mixed with WT CYPOR, only the Y181D CYPOR variant inhibited heme degradation by sequestering HO-1, whereas Y459H and V492E were unable to inhibit HO-1 activity suggesting that CYPOR variants might have differential binding affinities with redox partners. Titrating the CYPOR-HO-1 complex revealed that the optimal CYPOR:HO-1 ratio for activity was 1:2, lending evidence in support of productive HO-1 oligomerization, with higher ratios of CYPOR:HO-1 showing decreased activity. In conclusion, human POR mutations, shown to impact P450 activities, also result in varying degrees of diminished HO-1 activity, which may further complicate CYPOR deficiency.

Indexed as

Mutation, MissenseProtein MultimerizationFlavin-Adenine DinucleotideFlavin MononucleotideHemeHeme Oxygenase-1HumansMultienzyme ComplexesNADPH-Ferrihemoprotein ReductaseOxidoreductases Acting on CH-CH Group Donorsbiliverdin reductaseFlavin-Adenine DinucleotideFlavin MononucleotideHemeHeme Oxygenase-1HMOX1 protein, humanMultienzyme ComplexesNADPH-Ferrihemoprotein ReductaseOxidoreductases Acting on CH-CH Group Donors

Identifiers

PMID21741353
PMCPMC3516858
OpenAlexW2147361124

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.