Evidence map›Paper›PMID 19097988›Full record

ArticleAmerican journal of respiratory cell and molecular biology2009

Nickel mobilizes intracellular zinc to induce metallothionein in human airway epithelial cells.

Antonia A Nemec, George D Leikauf, Bruce R Pitt, Karla J Wasserloos, Aaron Barchowsky

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory cell and molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

15 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Article
  3. Trace Elements-Role in Joint Function and Impact on Joint Diseases.International journal of molecular sciences · 2025
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Metallomics : integrated biometal science · 2020
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Comparative analysis of MTF-1 binding sites between human and mouse.Mammalian genome : official journal of the International Mammalian Genome Society · 2010
    Article
  14. A turn-on fluorescent sensor for detecting nickel in living cells.Journal of the American Chemical Society · 2009
    Article
  15. Article
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 1 institution in 1 country.

Antonia A NemecDepartment of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.
George D Leikauf
Bruce R Pitt
Karla J Wasserloos
Aaron Barchowsky
University of Pittsburgh · US

Funding

Improving our mechanistic understanding of Electronic-cigarette, or vaping, product use-associated lung injuryU01ES015675 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEIKAUF, GEORGE DOUGLAS · 2006 to 2020
$8.9M
ZINC HOMEOSTASIS AND PULMONARY ENDOTHELIAL CELL INJURYR37HL065697 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PITT, BRUCE ROBERT · 2000 to 2009
$3.0M
REGULATION OF TRANSCRIPTIONAL COMPETENCE BY CHROMIUMR01ES010638 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BARCHOWSKY, AARON · 2001 to 2005
$1.4M
Growth Factor Protection in Acute Lung InjuryR01HL077763 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEIKAUF, GEORGE DOUGLAS · 2006 to 2009
$1.4M
Role of Metalloproteinases in Mucin Overproduction in COPDR01HL085655 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEIKAUF, GEORGE DOUGLAS · 2008 to 2011
$1.4M
NHLBI NIH HHS HL065697NHLBI NIH HHS HL077763NHLBI NIH HHS HL085655NIEHS NIH HHS ES015675NIEHS NIH HHS ES10638NIEHS NIH HHS U01 ES015675
6 · The paper itself

Abstract

We recently reported that induction of metallothionein (MT) was critical in limiting nickel (Ni)-induced lung injury in intact mice. Nonetheless, the mechanism by which Ni induces MT expression is unclear. We hypothesized that the ability of Ni to mobilize zinc (Zn) may contribute to such regulation and therefore, we examined the mechanism for Ni-induced MT2A expression in human airway epithelial (BEAS-2B) cells. Ni induced MT2A transcript levels and protein expression by 4 hours. Ni also increased the activity of a metal response element (MRE) promoter luciferase reporter construct, suggesting that Ni induces MRE binding of the metal transcription factor (MTF-1). Exposure to Ni resulted in the nuclear translocation of MTF-1, and Ni failed to induce MT in mouse embryonic fibroblasts lacking MTF-1. As Zn is the only metal known to directly bind MTF-1, we then showed that Ni increased a labile pool of intracellular Zn in cells as revealed by fluorescence-activated cell sorter using the Zn-sensitive fluorophore, FluoZin-3. Ni-induced increases in MT2A mRNA and MRE-luciferase activity were sensitive to the Zn chelator, TPEN, supporting an important role for Zn in mediating the effect of Ni. Although neither the source of labile Zn nor the mechanism by which Ni liberates labile Zn was apparent, it was noteworthy that Ni increased intracellular reactive oxygen species (ROS). Although both N-acetyl cysteine (NAC) and ascorbic acid (AA) decreased Ni-induced increases in ROS, only NAC prevented Ni-induced increases in MT2A mRNA, suggesting a special role for interactions of Ni, thiols, and Zn release.

Indexed as

AcetylcysteineAnimalsAntioxidantsAscorbic AcidBronchiCells, CulturedCell SeparationChelating AgentsChloridesDNA-Binding ProteinsEpithelial CellsEthylaminesFlow CytometryFluorescent DyesHumansMetallothioneinAcetylcysteineAntioxidantsAscorbic AcidChelating AgentsChloridesDNA-Binding ProteinsEthylaminesFluorescent DyesFluoZin-3MetallothioneinMT2A protein, humanNickelnickel sulfateN,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diaminePolycyclic CompoundsPyridinesPyrimidinesReactive Oxygen SpeciesRNA, MessengerTranscription Factor MTF-1Transcription Factorszinc chlorideZinc Compounds

Identifiers

PMID19097988
PMCPMC2701961
OpenAlexW2156278794

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.