Evidence map›Paper›PMID 22403404›Full record

Trial reportThe Journal of biological chemistry2012

Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and cellular IAP1/2 (cIAP1/2) in resistance to HIV-Vpr-induced apoptosis.

Aurelia Busca, Mansi Saxena, Ashok Kumar

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

44 citing papers in PubMed, 80 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Mcl-1 Protein and Viral Infections: A Narrative Review.International journal of molecular sciences · 2024
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. The Role of Bcl-xL Protein in Viral Infections.International journal of molecular sciences · 2021
    Review
  13. Article
  14. Review
  15. Article
  16. Protein ArginineViruses · 2020
    Article
  17. Review
  18. 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

3 authors at 2 institutions in 1 country.

Aurelia BuscaDepartment of Biochemistry, Microbiology and Immunology, Research Institute, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario K1H 8L1, Canada.
Mansi Saxena
Ashok Kumar
University of Ottawa · CAChildren's Hospital of Eastern Ontario · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Macrophages are resistant to HIV cytopathic effects, which contributes to viral persistence and reservoir formation. HIV viral protein R (Vpr) is a potent apoptosis-inducing agent for primary monocytes. Because the biologically active Vpr is found in serum and cerebrospinal fluid of HIV-infected patients, we investigated the apoptotic effect of Vpr on monocyte-derived macrophages and phorbol 12-myristate 13-acetate-activated THP1 macrophages. Our results show that primary monocytes and THP1 cells develop resistance to Vpr-induced apoptosis following differentiation into macrophages. To determine the effect of Vpr on the expression of antiapoptotic proteins, we show that in contrast to the undifferentiated cells, Vpr did not down-regulate the expression of antiapoptotic inhibitors of apoptosis (IAPs) and Bcl2 family members in macrophages, suggesting their involvement in resistance to Vpr-induced apoptosis. However, knocking down Bcl-xL and Mcl-1 proteins induced spontaneous apoptosis with no impact on susceptibility to Vpr-induced apoptosis. In contrast, down-regulation of cellular IAP1 (cIAP1) and cIAP2 by using siRNAs and SMAC (second mitochondria-derived activator of caspases) mimetic sensitized macrophages to Vpr-induced apoptosis. Overall, our results suggest that resistance to Vpr-induced apoptosis is specifically mediated by cIAP1/2 genes independent of Bcl-xL and Mcl-1, which play a key role in maintaining cell viability. Moreover, IAP modulation may be a potential strategy to eliminate HIV persistence in macrophages.

Indexed as

ApoptosisBaculoviral IAP Repeat-Containing 3 Proteinbcl-X ProteinCarcinogensCell DifferentiationCell Line, TumorFemaleHIV-1HIV InfectionsHumansInhibitor of Apoptosis ProteinsMacrophagesMaleMonocytesMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2Baculoviral IAP Repeat-Containing 3 ProteinBCL2L1 protein, humanbcl-X ProteinBIRC3 protein, humanCarcinogensInhibitor of Apoptosis ProteinsMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2Tetradecanoylphorbol AcetateUbiquitin-Protein Ligasesvpr Gene Products, Human Immunodeficiency Virusvpr protein, Human immunodeficiency virus 1

Identifiers

PMID22403404
PMCPMC3340279
OpenAlexW2073400944

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.