Evidence map›Paper›PMID 21808066›Full record

ArticleThe Journal of biological chemistry2011

Protection of neuronal calcium sensor 1 protein in cells treated with paclitaxel.

Jennifer H Benbow, Brenda DeGray, Barbara E Ehrlich

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

16 citing papers in PubMed, 32 citations in OpenAlex.

  1. Chemotherapy-induced peripheral neuropathy in breast cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026
    Review
  2. Article
  3. Measuring symptoms and toxicities: a 35-year experience.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2023
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. NCS-1 is a regulator of calcium signaling in health and disease.Biochimica et biophysica acta. Molecular cell research · 2018
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Inhibition of paclitaxel-induced decreases in calcium signaling.The Journal of biological chemistry · 2012
    Article
  15. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012
    Article
  16. 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.

Jennifer H BenbowDepartment of Pharmacology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520, USA.
Brenda DeGray
Barbara E Ehrlich
Yale University · US

Funding

Translational CoreP01DK057751 · NIDDK · YALE UNIVERSITY · PI NATHANSON, MICHAEL H · 2001 to 2020
$25.6M
Training Program in Investigative HepatologyT32DK007356 · NIDDK · YALE UNIVERSITY · PI MICHAEL H NATHANSON · 1986 to 2026
$7.4M
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 5T32DK007356-32NIDDK NIH HHS DK57751NIDDK NIH HHS DK61747NIDDK NIH HHS P01 DK057751NIDDK NIH HHS R01 DK061747NIDDK NIH HHS T32 DK007356
6 · The paper itself

Abstract

Paclitaxel (Taxol) is one of the most effective treatment options for patients suffering from a variety of cancers. A major side effect seen in a high percentage of patients treated with paclitaxel is irreversible peripheral neuropathy. We previously reported that prolonged treatment with paclitaxel activates a calcium-dependent enzyme, calpain, which degrades neuronal calcium sensor 1 (NCS-1) and subsequent loss of intracellular calcium signaling. Because it appears that activation of calpain is an early step in this destructive cascade, we proposed that inhibition of calpain will protect against the unwanted side effects of paclitaxel treatment. First, NCS-1 levels and intracellular calcium signaling were found to be protected by the presence of lactacystin, a protesome inhibitor. To reinforce the role of calpain in this process, we showed that increased concentrations of calpastatin, a naturally occurring calpain inhibitor, were protective. Next, we tested two mutated versions of NCS-1 developed with point mutations at the P2 position of the calpain cleavage site of NCS-1 to decrease the likelihood of NCS-1 degradation. One mutant was cleaved more favorably by calpain compared with NCS-1 WT, whereas the other mutant was less favorably cleaved. Expression of either mutated version of NCS-1 in neuroblastoma cells protected intracellular calcium signals from paclitaxel-induced changes. These results support our hypothesis that it is possible to protect cells from paclitaxel-induced degradation of NCS-1 by inhibiting calpain activity.

Indexed as

Calcium SignalingAcetylcysteineCalpainCell Line, TumorHumansMutationNeuroblastomaNeuronal Calcium-Sensor ProteinsNeuronsNeuropeptidesPaclitaxelPoint MutationProtease InhibitorsProtein IsoformsSignal TransductionThermodynamicsAcetylcysteineCalpainfrequenin calcium sensor proteinslactacystinNeuronal Calcium-Sensor ProteinsNeuropeptidesPaclitaxelProtease InhibitorsProtein Isoforms

Identifiers

PMID21808066
PMCPMC3186436
OpenAlexW2065496703

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.