Evidence map›Paper›PMID 20801127›Full record

ArticleJournal of molecular and cellular cardiology2010

Paclitaxel accelerates spontaneous calcium oscillations in cardiomyocytes by interacting with NCS-1 and the InsP3R.

Kun Zhang, Felix M Heidrich, Brenda DeGray, Wolfgang Boehmerle, Barbara E Ehrlich

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

38 citing papers in PubMed, 76 citations in OpenAlex.

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  12. Rutin and Hesperidin Alleviate Paclitaxel-Induced Nephrocardiotoxicity in Wistar RatsEvidence-based complementary and alternative medicine : eCAM · 2023
    Article
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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 3 institutions in 2 countries.

Kun ZhangDepartment of Pharmacology, Yale University, New Haven, CT 06520, USA.
Felix M Heidrich
Brenda DeGray
Wolfgang Boehmerle
Barbara E Ehrlich
Charité - Universitätsmedizin Berlin · DEYale University · USTU Dresden · DE

Funding

Translational CoreP01DK057751 · NIDDK · YALE UNIVERSITY · PI NATHANSON, MICHAEL H · 2001 to 2020
$25.6M
Regulation of cholangiocytes by InsP3 receptor isoformsR01DK061747 · NIDDK · YALE UNIVERSITY · PI EHRLICH, BARBARA E., NATHANSON, MICHAEL H · 2003 to 2012
$3.4M
NIDDK NIH HHS DK57751NIDDK NIH HHS DK61747NIDDK NIH HHS P01 DK057751NIDDK NIH HHS R01 DK061747
6 · The paper itself

Abstract

Paclitaxel (Taxol) is a microtubule-stabilizing compound that is used for cancer chemotherapy. However, Taxol administration is limited by serious side effects including cardiac arrhythmia, which cannot be explained by its microtubule-stabilizing effect. Recently, neuronal calcium sensor 1 (NCS-1), a calcium binding protein that modulates the inositol-1,4,5-trisphosphate receptor (InsP(3)R), was described as a binding partner of Taxol and as a substrate of calpain. We examined calcium signaling processes in cardiomyocytes after treatment with Taxol to investigate the basis of Taxol-induced cardiac arrhythmia. After treating isolated neonatal rat ventricular myocytes with a therapeutic concentration of Taxol for several hours live cell imaging experiments showed that the frequency of spontaneous calcium oscillations significantly increased. This effect was not mimicked by other tubulin-stabilizing agents. However, it was prevented by inhibiting the InsP(3)R. Taxol treated cells had increased expression of NCS-1, an effect also detectable after Taxol administration in vivo. Short hairpin RNA mediated knockdown of NCS-1 decreased InsP(3)R dependent intracellular calcium release, whereas Taxol treatment, that increased NCS-1 levels, increased InsP(3)R dependent calcium release. The effects of Taxol were ryanodine receptor independent. At the single channel level Taxol and NCS-1 mediated an increase in InsP(3)R activity. Calpain activity was not affected by Taxol in cardiomyocytes suggesting a calpain independent signaling pathway. In short, our study shows that Taxol impacts calcium signaling and calcium oscillations in cardiomyocytes through NCS-1 and the InsP(3)R.

Indexed as

AgingAnimalsAnimals, NewbornCalcium SignalingCalpainEnzyme ActivationInositol 1,4,5-Trisphosphate ReceptorsMiceMice, Inbred C57BLMyocardiumMyocytes, CardiacNeuronal Calcium-Sensor ProteinsNeuropeptidesPaclitaxelProtein BindingProtein Processing, Post-TranslationalCalpainfrequenin calcium sensor proteinsInositol 1,4,5-Trisphosphate ReceptorsNeuronal Calcium-Sensor ProteinsNeuropeptidesPaclitaxel

Identifiers

PMID20801127
PMCPMC2965648
OpenAlexW2055745456

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.