Evidence map›Paper›PMID 12065515›Full record

ArticleInfection and immunity2002

Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in Leishmania amazonensis amastigotes.

Philippe Holzmuller, Denis Sereno, Mireille Cavaleyra, Isabelle Mangot, Sylvie Daulouede, Philippe Vincendeau, Jean-Loup Lemesre

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2002. 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
5.4field-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

38 citing papers in PubMed, 108 citations in OpenAlex.

  1. An inclusive assessment of apoptosis mechanisms inCurrent research in parasitology & vector-borne diseases · 2025
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  5. Insecticidal, Antimalarial, and Antileishmanial Effects of Royal Jelly and Its Three Main Fatty Acids,Evidence-based complementary and alternative medicine : eCAM · 2022
    Article
  6. Antileishmanial Activity ofMicroorganisms · 2021
    Article
  7. Article
  8. Review
  9. (De)glutamylation and cell death in Leishmania parasites.PLoS neglected tropical diseases · 2019
    Article
  10. Cell death in Leishmania.Parasite (Paris, France) · 2019
    Review
  11. Oxidative Stress-Mediated Overexpression of Uracil DNA Glycosylase inOxidative medicine and cellular longevity · 2018
    Article
  12. Article
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  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

7 authors at 2 institutions in 2 countries.

Philippe HolzmullerUR 008 Pathogénie des Trypanosomatidés, Institut de Recherche pour le Développement, 34032 Montpellier Cedex 1, France.
Denis Sereno
Mireille Cavaleyra
Isabelle Mangot
Sylvie Daulouede
Philippe Vincendeau
Jean-Loup Lemesre
Institut de Recherche pour le Développement · BJUniversité de Bordeaux · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Resistance to leishmanial infections depends on intracellular parasite killing by activated host macrophages through the L-arginine-nitric oxide (NO) metabolic pathway. Here we investigate the cell death process induced by NO for the intracellular protozoan Leishmania amazonensis. Exposure of amastigotes to moderate concentrations of NO-donating compounds (acidified sodium nitrite NaNO(2) or nitrosylated albumin) or to endogenous NO produced by lipopolysaccharide or gamma interferon treatment of infected macrophages resulted in a dramatic time-dependent cell death. The combined use of several standard DNA status analysis techniques (including electrophoresis ladder banding patterns, YOPRO-1 staining in flow cytofluorometry, and in situ recognition of DNA strand breaks by TUNEL [terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling] assay) revealed a rapid and extensive fragmentation of nuclear DNA in both axenic and intracellular NO-treated amastigotes of L. amazonensis. Despite some similarities to apoptosis, the nuclease activation responsible for characteristic DNA degradation was not under the control of caspase activity as indicated by the lack of involvement of cell-permeable inhibitors of caspases and cysteine proteases. In contrast, exposure of NO-treated amastigotes with specific proteasome inhibitors, such as lactacystin or calpain inhibitor I, markedly reduced the induction of the NO-mediated apoptosis-like process. These data strongly suggest that NO-induced oligonucleosomal DNA fragmentation in Leishmania amastigotes is, at least in part, regulated by noncaspase proteases of the proteasome. The determination of biochemical pathways leading up to cell death might ultimately allow the identification of new therapeutic targets.

Indexed as

DNA FragmentationDNA, ProtozoanAcetylcysteineAnimalsApoptosisCysteine EndopeptidasesCysteine Proteinase InhibitorsFemaleGlycoproteinsKineticsLeishmania mexicanaLeupeptinsMiceMice, Inbred BALB CMultienzyme ComplexesNitric OxideAcetylcysteinecalpain inhibitorscarbobenzoxy-leucyl-leucyl-norvalinalCysteine EndopeptidasesCysteine Proteinase InhibitorsDNA, ProtozoanGlycoproteinslactacystinLeupeptinsMultienzyme ComplexesNitric OxideNitric Oxide DonorsProteasome Endopeptidase ComplexSodium Nitrite

Identifiers

PMID12065515
PMCPMC128075
OpenAlexW2127694821

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.