Evidence map›Paper›PMID 21289302›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2011

Human TMEM30a promotes uptake of antitumor and bioactive choline phospholipids into mammalian cells.

Rui Chen, Erin Brady, Thomas M McIntyre

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

21 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Context-Dependent Role of Oxidized Lipids and Lipoproteins in Inflammation.Trends in endocrinology and metabolism: TEM · 2017
    Review
  10. Review
  11. Article
  12. Review
  13. P4-ATPases: lipid flippases in cell membranes.Pflugers Archiv : European journal of physiology · 2014
    Review
  14. Lipids and cell death in yeast.FEMS yeast research · 2014
    Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  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 1 institution in 1 country.

Rui ChenDepartment of Cell Biology, Cleveland Clinic, Cleveland, OH 44195, USA.
Erin Brady
Thomas M McIntyre
Cleveland Clinic · US

Funding

ROLE OF MICROPARTICLES IN THE ANTI-PHOSPHOLIPID SYNDROMEP50HL081011 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS · 2006 to 2010
$12.9M
REGULATION OF MONOCYTE 15-LIPOXYGENASE EXPRESSIONP01HL087018 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS M · 2007 to 2011
$11.4M
Circulating Age-related Lipid Mediators in ThrombosisR01HL092747 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS M · 2007 to 2010
$2.2M
Systemic Oxidized Phospholipids in Mitochondrial Dysfunction of Alcoholic InjuryR01AA017748 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS M · 2008 to 2012
$1.9M
NHLBI NIH HHS HL092747NHLBI NIH HHS P01 HL087018NHLBI NIH HHS P50 HL081011NHLBI NIH HHS R01 HL092747NIAAA NIH HHS AA017748NIAAA NIH HHS R01 AA017748
6 · The paper itself

Abstract

Antitumor alkylphospholipids initiate apoptosis in transformed HL-60 and Jurkat cells while sparing their progenitors. 1-O-Alkyl-2-carboxymethyl-sn-glycero-3-phosphocholine (Edelfosine) like other short-chained phospholipids--inflammatory platelet-activating factor (PAF) and apoptotic oxidatively truncated phospholipids--are proposed to have intracellular sites of action, yet a conduit for these choline phospholipids into mammalian cells is undefined. Edelfosine is also accumulated by Saccharomyces cerevisiae in a process requiring the membrane protein Lem3p, and the human genome contains a Lem3p homolog TMEM30a. We show that import of choline phospholipids into S. cerevisiae ΔLem3 is partially reconstituted by human TMEM30a and by Lem3p-TMEM30a chimeras, showing the proteins are orthologous. TMEM30a-GFP chimeras expressed in mammalian cells localized in plasma membranes, as well as internal organelles, and ectopic TMEM30a expression promoted uptake of exogenous choline and ethanolamine phospholipids. Short hairpin RNA knockdown of TMEM30a reduced fluorescent choline phospholipid and [(3)H]PAF import. This knockdown also reduced mitochondrial depolarization from exogenous Edelfosine or the mitotoxic oxidatively truncated phospholipid azelaoyl phosphatidylcholine, and the knockdown reduced apoptosis in response to these two phospholipids. These results show that extracellular choline phospholipids with short sn-2 residues can have intracellular roles and sites of metabolism because they are transport substrates for a TMEM30a phospholipid import system. Variation in this mechanism could limit sensitivity to short chain choline phospholipids such as Edelfosine, PAF, and proapoptotic phospholipids.

Indexed as

Amino Acid SequenceAnimalsAntineoplastic AgentsBiological Transport, ActiveCell Line, TransformedCHO CellsCholineCricetinaeCricetulusDrug Resistance, NeoplasmHep G2 CellsHL-60 CellsHumansJurkat CellsMembrane ProteinsMembrane Transport ProteinsAntineoplastic AgentsCDC50 protein, S cerevisiaeCholineLem3 protein, S cerevisiaeMembrane ProteinsMembrane Transport ProteinsMutant Chimeric ProteinsPhospholipidsSaccharomyces cerevisiae ProteinsTMEM30a protein, human

Identifiers

PMID21289302
PMCPMC3073457
OpenAlexW1595798721

What OpenQuestion holds

Textmetadata
LicenceTDM
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.