Evidence map›Paper›PMID 34867397›Full record

ArticleFrontiers in pharmacology2021

Effects of Diminished NADPH:cytochrome P450 Reductase in Human Hepatocytes on Lipid and Bile Acid Homeostasis.

Tamara Heintze, Denise Wilhelm, Thierry Schmidlin, Ute Hofmann, Ulrich M Zanger, Matthias Schwab, Kathrin Klein

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 28% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Physiological Functions and Pathological Roles of PXR.Journal of the Endocrine Society · 2025
    Review
  6. The Central Role of Cytochrome P450 Reductase (CPR) in Hyperoxic Lung Injury.Expert opinion on drug metabolism & toxicology · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
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

7 authors at 2 institutions in 2 countries.

Tamara HeintzeMargarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Denise WilhelmMargarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Thierry SchmidlinMargarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Ute HofmannMargarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Ulrich M ZangerMargarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Matthias SchwabMargarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Kathrin KleinMargarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
University of Tübingen · DEDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

nadphcytochrome P450 oxidoreductase (POR) is the obligate electron donor for microsomal cytochrome P450 (CYP) enzymes involved in the biosynthesis of endogenous substances like bile acids and other steroids as well as in the oxidative metabolism of xenobiotics. P450 oxidoreductase also supports other redox enzymes in fatty acid and cholesterol pathways. Recently, we have established CRISPR/Cas9-mediated POR knockdown in a human hepatic cell model, HepaRG, and demonstrated the differential effects of limited POR expression on CYP activity. The aim of the present work was to systematically investigate the impact of POR knockdown with a focus on the expression of ADME (absorption, distribution, metabolism, and excretion) genes and related regulators. Functional consequences have been assessed using quantitative mass spectrometry for targeted metabolomics covering bile acids, and cholesterol and its precursors, and for untargeted proteomics. In addition to the previously described alteration of RNA expression of CYP genes, we showed significant downregulation of transcriptional regulators of drug metabolism and transport, including NR1I3 (CAR), NR1I2 (PXR), NR1H4 (FXR), and NR1H3 (LXRα) in cells with

Indexed as

bile acid metabolismcholesterol biosynthesisCRISPR/Cas9HepaRGNADPH cytochrome P450 reductaseproteomics

Identifiers

PMID34867397
PMCPMC8634102
OpenAlexW3214470396

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.