Evidence map›Paper›PMID 25015959›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2014

Sex-dependent, zinc-induced dephosphorylation of phospholamban by tissue-nonspecific alkaline phosphatase in the cardiac sarcomere.

Yuan Wang, Nicole M Bishop, Douglas J Taatjes, Sonoko Narisawa, José Luis Millán, Bradley M Palmer

Open access · greenAbstract readComparative Study
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 33% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Review
  2. Article
  3. 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

6 authors at 3 institutions in 1 country.

Yuan WangDepartment of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont;
Nicole M BishopMicroscopy Imaging Center, University of Vermont, Burlington, Vermont; and.
Douglas J TaatjesMicroscopy Imaging Center, University of Vermont, Burlington, Vermont; and.
Sonoko NarisawaSanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California.
José Luis MillánSanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California.
Bradley M PalmerDepartment of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont; bmpalmer@uvm.edu.
Imaging Center · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of Vermont · US

Funding

MOLECULAR PATHOGENESIS/TREATMENT OF HYPOPHOSPHATASIAR01DE012889 · NIDCR · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 1999 to 2020
$9.2M
Cardiomyocyte Zinc and its Regulation of Contraction-Relaxation FunctionR01HL086902 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI PALMER, BRADLEY M · 2008 to 2012
$1.9M
NHLBI NIH HHS HL-086902NIDCR NIH HHS DE-12889
6 · The paper itself

Abstract

We have previously reported that Zn(2+) infused into the coronary arteries of isolated rat hearts leads to the potent dephosphorylation of phospholamban (PLB) as well as a noticeable but less potent dephosphorylation of the ryanodine receptor 2. We hypothesized in the present study that a Zn(2+)-activated phosphatase is located in the vicinity of the sarcoplasmic reticulum (SR) where PLB and ryanodine receptor 2 reside. We report here the novel finding of tissue-nonspecific alkaline phosphatase (TNAP), a zinc-dependent enzyme, localized to the SR in the cardiac sarcomere of mouse myocardium. TNAP activity was enhanced by injection of Zn acetate into a tail vein before harvesting the heart and imaged using electron microscopy of electron dense deposits indicative of the hydrolysis of exogenous β-glycerophosphate. TNAP activity was observed localized to the ends of the Z-line corresponding to SR and was qualitatively more visible in myocardium of males compared with females. Correspondingly, PLB phosphorylation status was potently reduced in myocardium of males injected with Zn acetate, whereas there was no apparent effect of Zn acetate injection on PLB phosphorylation in females. Surprisingly, Western blot analysis of TNAP content suggested a significantly lower TNAP content in males compared with females. These data suggest that TNAP plays a role in governing the phosphorylation status of calcium handling proteins in the SR. Furthermore, the content and activity of TNAP are differentially regulated between the sexes and thus may account for some sex differences in cardiopathologies associated with calcium handling.

Indexed as

Alkaline PhosphataseAnimalsCalciumCalcium-Binding ProteinsFemaleInjections, IntravenousMaleMiceMyocytes, CardiacPhospholambanPhosphorylationSarcomeresSex FactorsZinc AcetateAlkaline PhosphataseALPL protein, mouseCalciumCalcium-Binding ProteinsPhospholambanZinc Acetateenzymesarcoplasmic reticulumzinc

Identifiers

PMID25015959
PMCPMC4166743
OpenAlexW2030213482

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.