Evidence map›Paper›PMID 23631432›Full record

ArticleACS chemical biology2013

Quantification of cellular poly(ADP-ribosyl)ation by stable isotope dilution mass spectrometry reveals tissue- and drug-dependent stress response dynamics.

Rita Martello, Aswin Mangerich, Sabine Sass, Peter C Dedon, Alexander Bürkle

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
–field-weighted citation impact, top 96% 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

38 citing papers in PubMed, 0 citations in OpenAlex.

  1. Article
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  9. Review
  10. Article
  11. A Double-Edged Sword: The Two Faces of PARylation.International journal of molecular sciences · 2022
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. ADPriboDB v2.0: An Updated Database of ADP-ribosylated Proteins.bioRxiv : the preprint server for biology · 2020
    Article
  19. Article
  20. Review
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

5 authors at 3 institutions in 2 countries.

Rita MartelloMolecular Toxicology Group and ‡Konstanz Research School Chemical Biology, University of Konstanz , Konstanz 78464, Germany.
Aswin Mangerich
Sabine Sass
Peter C Dedon
Alexander Bürkle
Center for Environmental Health · USMassachusetts Institute of Technology · USUniversity of Konstanz · DE

Funding

TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
Reaction and Diffusion of NO in Biological SystemsP01CA026731 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TANNENBAUM, STEVEN R · 1985 to 2018
$25.4M
NCI NIH HHS CA026731NCI NIH HHS P01 CA026731NIEHS NIH HHS ES002109NIEHS NIH HHS P30 ES002109
6 · The paper itself

Abstract

Poly(ADP-ribosyl)ation is an essential post-translational modification with the biopolymer poly(ADP-ribose) (PAR). The reaction is catalyzed by poly(ADP-ribose) polymerases (PARPs) and plays key roles in cellular physiology and stress response. PARP inhibitors are currently being tested in clinical cancer treatment, in combination therapy, or as monotherapeutic agents by inducing synthetic lethality. We have developed an accurate and sensitive bioanalytical platform based on isotope dilution mass spectrometry in order to quantify steady-state and stress-induced PAR levels in cells and tissues and to characterize pharmacological properties of PARP inhibitors. In contrast to existing PAR-detection techniques, the LC-MS/MS method uses authentic isotope-labeled standards, which provide unequivocal chemical specificity to quantify cellular PAR in absolute terms with femtomol sensitivity. Using this platform we analyzed steady-state levels as well as stress-induced dynamics of poly(ADP-ribosyl)ation in a series of biological systems including cancer cell lines, mouse tissues, and primary human lymphocytes. Our results demonstrate a rapid and transient stress-induced increase in PAR levels by >100-fold in a dose- and time-dependent manner with significant differences between cell types and individual human lymphocyte donors. Furthermore, ex vivo pharmacodynamic studies in human lymphocytes provide new insight into pharmacological properties of clinically relevant PARP inhibitors. Finally, we adapted the LC-MS/MS method to quantify poly(ADP-ribosyl)ation in solid tissues and identified tissue-dependent associations between PARP1 expression and PAR levels in a series of different mouse organs. In conclusion, this study demonstrates that mass spectrometric quantification of cellular poly(ADP-ribosyl)ation has a wide range of applications in basic research as well as in drug development.

Indexed as

IsotopesStress, PhysiologicalAnimalsCell Line, TumorChromatography, High Pressure LiquidDose-Response Relationship, DrugEnzyme InhibitorsFluorescent Antibody TechniqueHumansLimit of DetectionLymphocytesMass SpectrometryMiceMolecular StructurePoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesEnzyme InhibitorsIsotopesPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) Polymerases

Identifiers

PMID23631432
PMCPMC3795969
OpenAlexW1600047105

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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.