Evidence map›Paper›PMID 17283068›Full record

ArticleThe Journal of biological chemistry2007

Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells.

Jacqueline M Kraveka, Li Li, Zdzislaw M Szulc, Jacek Bielawski, Besim Ogretmen, Yusuf A Hannun, Lina M Obeid, Alicja Bielawska

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

105 citing papers in PubMed, 174 citations in OpenAlex.

  1. Trial
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  16. Review
  17. Article
  18. Dihydroceramide desaturase 1 (DES1) promotes anchorage-independent survival downstream of HER2-driven glucose uptake and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  19. Article
  20. Fenretinide in Cancer and Neurological Disease: A Two-Face Janus Molecule.International journal of molecular sciences · 2022
    Review

45 more citing papers are in PubMed but not listed here.

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

8 authors at 1 institution in 1 country.

Jacqueline M KravekaDivision of Hematology/Oncology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA. kravekjm@musc.edu
Li Li
Zdzislaw M Szulc
Jacek Bielawski
Besim Ogretmen
Yusuf A Hannun
Lina M Obeid
Alicja Bielawska
Medical University of South Carolina · US

Funding

Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Daniel Canals · 2003 to 2026
$30.8M
THE ROLE OF LACTOSYLCERAMIDE IN RENAL AGING AND DISEASEP20RR017677 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MAO, CUNGUI · 2002 to 2011
$23.4M
Ceramide Signaling in the Regulation of Head & Neck Cancer Cell Death and TherapyR01DE016572 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2005 to 2025
$7.4M
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR018823 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2003 to 2003
$2.9M
Mitochondrial Ceramide in Chemotherapy-induced ApoptosisR01AG016583 · NIA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OBEID, LINA M · 1998 to 2010
$2.7M
Role of Ceramide in Human Neuroblastoma DifferentiationK01CA100767 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KRAVEKA, JACQUELINE M · 2003 to 2007
$685k
NCI NIH HHS K01 CA100767NCI NIH HHS L40 CA110721NCI NIH HHS P01 CA097132NCRR NIH HHS C06 RR018823NCRR NIH HHS P20 RR017677NIA NIH HHS R01 AG016583NIDCR NIH HHS R01 DE016572
6 · The paper itself

Abstract

The role of dihydroceramide desaturase as a key enzyme in the de novo pathway of ceramide generation was investigated in human neuroblastoma cells (SMS-KCNR). A novel assay using water-soluble analogs of dihydroceramide, dihydroceramidoids (D-erythro-dhCCPS analogs), was used to measure desaturase activity in situ. Conversion of D-erythro-2-N-[12'-(1''-pyridinium)-dodecanoyl]-4,5-dihydrosphingosine bromide (C(12)-dhCCPS) to its 4,5-desaturated counterpart, D-erythro-2-N-[12'-(1''-pyridinium)dodecanoyl]sphingosine bromide (C(12)-CCPS), was determined by liquid chromatography/mass spectrometry analysis. The validity of the assay was confirmed using C(8)-cyclopropenylceramide, a competitive inhibitor of dihydroceramide desaturase. A human homolog (DEGS-1) of the Drosophila melanogaster des-1 gene was recently identified and reported to have desaturase activity. Transfection of SMS-KCNR cells with small interfering RNA to DEGS-1 significantly blocked the conversion of C(12)-dhCCPS to C(12)-CCPS. The associated accumulation of endogenous dihydroceramides confirmed DEGS-1 as the main active dihydroceramide desaturase in these cells. The partial loss of DEGS-1 inhibited cell growth, with cell cycle arrest at G(0)/G(1). This was accompanied by a significant decrease in the amount of phosphorylated retinoblastoma protein. This hypophosphorylation was inhibited by tautomycin and not by okadaic acid, suggesting the involvement of protein phosphatase 1. Additionally, we found that treatment of SMS-KCNR cells with fenretinide inhibited desaturase activity in a dose-dependent manner. An increase in dihydroceramides (but not ceramides) paralleled this process as measured by liquid chromatography/mass spectrometry. There were no effects on the mRNA or protein levels of DEGS-1, suggesting that fenretinide acts at the post-translational level as an inhibitor of this enzyme. Tautomycin was also able to block the hypophosphorylation of the retinoblastoma protein observed upon fenretinide treatment. These findings suggest a novel biological function for dihydroceramides.

Indexed as

Cell CycleBase SequenceBlotting, WesternCell DivisionCell Line, TumorCeramidesChromatography, LiquidDNA PrimersFenretinideHumansMass SpectrometryNeuroblastomaOxidoreductasesPhosphorylationReverse Transcriptase Polymerase Chain ReactionRNA InterferenceCeramidesdihydroceramide desaturaseDNA PrimersFenretinideOxidoreductasesRNA, Small Interfering

Identifiers

PMID17283068
PMCPMC2084375
OpenAlexW2000099744

What OpenQuestion holds

Textmetadata
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.