Merck
  • Home
  • Search Results
  • Activated platelets rescue apoptotic cells via paracrine activation of EGFR and DNA-dependent protein kinase.

Activated platelets rescue apoptotic cells via paracrine activation of EGFR and DNA-dependent protein kinase.

Cell death & disease (2014-09-12)
A E-L Au, M Sashindranath, R J Borg, O Kleifeld, R K Andrews, E E Gardiner, R L Medcalf, A L Samson
ABSTRACT

Platelet activation is a frontline response to injury, not only essential for clot formation but also important for tissue repair. Indeed, the reparative influence of platelets has long been exploited therapeutically where application of platelet concentrates expedites wound recovery. Despite this, the mechanisms of platelet-triggered cytoprotection are poorly understood. Here, we show that activated platelets accumulate in the brain to exceptionally high levels following injury and release factors that potently protect neurons from apoptosis. Kinomic microarray and subsequent kinase inhibitor studies showed that platelet-based neuroprotection relies upon paracrine activation of the epidermal growth factor receptor (EGFR) and downstream DNA-dependent protein kinase (DNA-PK). This same anti-apoptotic cascade stimulated by activated platelets also provided chemo-resistance to several cancer cell types. Surprisingly, deep proteomic profiling of the platelet releasate failed to identify any known EGFR ligand, indicating that activated platelets release an atypical activator of the EGFR. This study is the first to formally associate platelet activation to EGFR/DNA-PK--an endogenous cytoprotective cascade.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Formic acid solution, BioUltra, 1.0 M in H2O
Sigma-Aldrich
Formic acid, puriss., meets analytical specifications of DAC, FCC, 98.0-100%
Sigma-Aldrich
Formic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥98%
Sigma-Aldrich
Ammonium bicarbonate, ReagentPlus®, ≥99.0%
Sigma-Aldrich
Formic acid, reagent grade, ≥95%
Sigma-Aldrich
Formic acid, ACS reagent, ≥88%
Sigma-Aldrich
Formic acid, ACS reagent, ≥96%
Supelco
Tris(2-carboxyethyl)phosphine hydrochloride solution, 0.5 M, pH 7.0(aqueous solution; pH was adjusted with ammonium hydroxide)
SAFC
Iodoacetamide
Etoposide, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Iodoacetamide, ≥99% (NMR), crystalline
Sigma-Aldrich
Formic acid, ≥95%, FCC, FG
Sigma-Aldrich
Dextrose, meets EP, BP, JP, USP testing specifications, anhydrous
Sigma-Aldrich
Etoposide, synthetic, 95.0-105.0%, powder
Sigma-Aldrich
Iodoacetamide, BioUltra
Sigma-Aldrich
Z-Leu-Leu-Leu-al, ≥90% (HPLC)
Sigma-Aldrich
Ammonium bicarbonate, BioUltra, ≥99.5% (T)
Sigma-Aldrich
Iodoacetamide, Single use vial of 56 mg
Supelco
Dextrose, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Tris(2-carboxyethyl)phosphine hydrochloride, powder
Sigma-Aldrich
Sodium chloride solution, 5 M
Sigma-Aldrich
3-Morpholinosydnonimine hydrochloride, (consistent with structure, NMR)
Sigma-Aldrich
Sodium chloride solution, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
D-(+)-Glucose, ACS reagent
Sigma-Aldrich
D-(+)-Glucose, BioXtra, ≥99.5% (GC)
Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC)
Sigma-Aldrich
D-(+)-Glucose, Hybri-Max, powder, BioReagent, suitable for hybridoma
Sigma-Aldrich
D-(+)-Glucose, suitable for mouse embryo cell culture, ≥99.5% (GC)
Sigma-Aldrich
D-(+)-Glucose, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.5%
Sigma-Aldrich
HEPES, ≥99.5% (titration)