Evidence map›Paper›PMID 10593923›Full record

ArticleThe Journal of biological chemistry1999

Inhibition of calpain blocks platelet secretion, aggregation, and spreading.

K Croce, R Flaumenhaft, M Rivers, B Furie, B C Furie, I M Herman, D A Potter

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

33 citing papers in PubMed, 127 citations in OpenAlex.

  1. Trial
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  7. Article
  8. The C2 domain of calpain 5 contributes to enzyme activation and membrane localization.Biochimica et biophysica acta. Molecular cell research · 2021
    Article
  9. Article
  10. Procoagulant Phosphatidylserine-Exposing PlateletsFrontiers in cardiovascular medicine · 2020
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Protein degradation systems in platelets.Thrombosis and haemostasis · 2013
    Review
  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

7 authors at 4 institutions in 1 country.

K CroceDepartment of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
R Flaumenhaft
M Rivers
B Furie
B C Furie
I M Herman
D A Potter
Beth Israel Deaconess Medical Center · USTufts University · USHoward Hughes Medical Institute · USTufts Medical Center · US

Funding

PILOT AND FEASIBILITY STUDIESP30DK034928 · NIDDK · TUFTS MEDICAL CENTER · PI PLAUT, ANDREW GEORGE · 1986 to 2007
$8.5M
STRUCTURE OF THE VITAMIN K-DEPENDENT CARBOXYLASEP01HL042443 · NHLBI · TUFTS MEDICAL CENTER · PI FURIE, BARBARA C · 1989 to 2003
$7.4M
SELECTIN LIGANDS IN LEUKOCYTE BIOLOGY AND INFLAMMATIONR01HL051926 · NHLBI · TUFTS MEDICAL CENTER · PI FURIE, BRUCE · 1995 to 2008
$3.6M
REGULATION OF ISOACTIN DYNAMICS IN LIVING CELLSR01GM055110 · NIGMS · TUFTS UNIVERSITY BOSTON · PI HERMAN, IRA M · 1997 to 2000
$288k
FUNCTIONAL ANALYSIS OF TRANSCRIPTION FACTORS IN HIV-1K08CA001562 · NCI · TUFTS MEDICAL CENTER · PI POTTER, DAVID ALEXANDER · 1991 to 1996
–
NCI NIH HHS K08 CA001562NCI NIH HHS K08-CA 1562NHLBI NIH HHS P01 HL042443NHLBI NIH HHS R01 HL051926NIDDK NIH HHS P30 DK034928NIDDK NIH HHS P30 DK34928NIGMS NIH HHS GM55110
6 · The paper itself

Abstract

Previous studies have indicated that the Ca(2+)-dependent protease, calpain, is activated in platelets within 30-60 s of thrombin stimulation, but specific roles of calpain in platelets remain to be identified. To directly test the functions of calpain during platelet activation, a novel strategy was developed for introducing calpain's specific biological inhibitor, calpastatin, into platelets prior to activation. This method involves treatment of platelets with a fusion peptide, calpastat, consisting of the cell-penetrating signal sequence from Kaposi's fibroblast growth factor connected to a calpain-inhibiting consensus sequence derived from calpastatin. Calpastat specifically inhibits thrombin peptide (SFLLR)-induced alpha-granule secretion (IC(50) = 20 microM) during the first 30 s of activation, thrombin-induced platelet aggregation (IC(50) = 50 microM), and platelet spreading on glass surfaces (IC(50) = 34 microM). Calpastat-Ala, a mutant peptide in which alanine is substituted at conserved calpastatin residues, lacks calpain inhibitory activity and fails to inhibit secretion, aggregation, or spreading. The peptidyl calpain inhibitors calpeptin, MDL 28,170 (MDL) and E64d also inhibit secretion, aggregation and spreading, but require 3-10-fold higher concentrations than calpastat for biological activity. Together, these findings demonstrate that calpain regulates platelet secretion, aggregation, and spreading and indicate that calpain plays an earlier role in platelet activation following thrombin receptor stimulation than had been previously detected.

Indexed as

Platelet AggregationAmino Acid SequenceBlood PlateletsCalcium-Binding ProteinsCalpainHumansMolecular Sequence DataMutationPeptide FragmentsPlatelet AdhesivenessCalcium-Binding ProteinsCalpaincalpastatinPeptide Fragments

Identifiers

PMID10593923
PMCPMC2727653
OpenAlexW2066141526

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.