Evidence map›Paper›PMID 19809895›Full record

ArticleCell stress & chaperones2010

The topical antimicrobial zinc pyrithione is a heat shock response inducer that causes DNA damage and PARP-dependent energy crisis in human skin cells.

Sarah D Lamore, Christopher M Cabello, Georg T Wondrak

Open access · bronzeAbstract read
In one paragraph

Article in Cell stress & chaperones, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.8field-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

28 citing papers in PubMed, 73 citations in OpenAlex.

  1. Metabolic Atlas of Human Eyelid Infiltrative Basal Cell Carcinoma.Investigative ophthalmology & visual science · 2025
    Article
  2. Article
  3. Review
  4. Bioactive small-molecule constituents of Lao plants.Journal of medicinal plant research · 2021
    Article
  5. Article
  6. Targeted Delivery of Zinc Pyrithione to Skin Epithelia.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Phytotoxicity evaluation of some commonly used shampoos using Brassica napus L.Environmental science and pollution research international · 2015
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

3 authors at 1 institution in 1 country.

Sarah D LamoreDepartment of Pharmacology and Toxicology, College of Pharmacy, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
Christopher M Cabello
Georg T Wondrak
University of Arizona · US

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
Training in Environmental Toxicology of Human DiseaseT32ES007091 · NIEHS · UNIVERSITY OF ARIZONA · PI Nathan J Cherrington · 1985 to 2026
$10.7M
Targeting Glycolytic Control of Melanoma Cell SurvivalR01CA122484 · NCI · UNIVERSITY OF ARIZONA · PI WONDRAK, GEORG T · 2007 to 2011
$1.3M
NCI NIH HHS CA023074NCI NIH HHS P30 CA023074NCI NIH HHS R01 CA122484NCI NIH HHS R01CA122484NIEHS NIH HHS ES007091NIEHS NIH HHS ES06694NIEHS NIH HHS P30 ES006694NIEHS NIH HHS T32 ES007091
6 · The paper itself

Abstract

The differentiated epidermis of human skin serves as an essential barrier against environmental insults from physical, chemical, and biological sources. Zinc pyrithione (ZnPT) is an FDA-approved microbicidal agent used worldwide in clinical antiseptic products, over-the-counter topical antimicrobials, and cosmetic consumer products including antidandruff shampoos. Here we demonstrate for the first time that cultured primary human skin keratinocytes and melanocytes display an exquisite vulnerability to nanomolar concentrations of ZnPT resulting in pronounced induction of heat shock response gene expression and impaired genomic integrity. In keratinocytes treated with nanomolar concentrations of ZnPT, expression array analysis revealed massive upregulation of genes encoding heat shock proteins (HSPA6, HSPA1A, HSPB5, HMOX1, HSPA1L, and DNAJA1) further confirmed by immunodetection. Moreover, ZnPT treatment induced rapid depletion of cellular ATP levels and formation of poly(ADP-ribose) polymers. Consistent with an involvement of poly(ADP-ribose) polymerase (PARP) in ZnPT-induced energy crisis, ATP depletion could be antagonized by pharmacological inhibition of PARP. This result was independently confirmed using PARP-1 knockout mouse embryonic fibroblasts that were resistant to ATP depletion and cytotoxicity resulting from ZnPT exposure. In keratinocytes and melanocytes, single-cell gel electrophoresis and flow cytometric detection of gamma-H2A.X revealed rapid induction of DNA damage in response to ZnPT detectable before general loss of cell viability occurred through caspase-independent pathways. Combined with earlier experimental evidence that documents penetration of ZnPT through mammalian skin, our findings raise the possibility that this topical antimicrobial may target and compromise keratinocytes and melanocytes in intact human skin.

Indexed as

Anti-Infective AgentsDNA DamageKeratinocytesMelanocytesOrganometallic CompoundsPyridinesSkinAdenosine TriphosphateAdministration, TopicalAnimalsFibroblastsGene ExpressionHeat-Shock ProteinsHeat-Shock ResponseHumansKeratolytic AgentsAdenosine TriphosphateAnti-Infective AgentsHeat-Shock ProteinsKeratolytic AgentsOrganometallic CompoundsPoly(ADP-ribose) PolymerasesPyridinespyrithione zinc

Identifiers

PMID19809895
PMCPMC2866994
OpenAlexW2002665603

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.