Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1 - 13 |
| Number of pages | 13 |
| Journal | Cell Death and Disease |
| Volume | 5 |
| DOIs | |
| Publication status | Published - 2014 |
Cite this
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Activated platelets rescue apoptotic cells via paracrine activation of EGFR and DNA-dependent protein kinase. / Au, Amanda E-Ling; Sashindranath, Maithili; Borg, Rachael Jade; Kleifeld, Oded; Andrews, Robert Keith; Gardiner, Elizabeth Ellen; Medcalf, Robert Lindsay; Samson, Andre Laval.
In: Cell Death and Disease, Vol. 5, 2014, p. 1 - 13.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Activated platelets rescue apoptotic cells via paracrine activation of EGFR and DNA-dependent protein kinase
AU - Au, Amanda E-Ling
AU - Sashindranath, Maithili
AU - Borg, Rachael Jade
AU - Kleifeld, Oded
AU - Andrews, Robert Keith
AU - Gardiner, Elizabeth Ellen
AU - Medcalf, Robert Lindsay
AU - Samson, Andre Laval
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.nature.com/cddis/journal/v5/n9/pdf/cddis2014373a.pdf
U2 - 10.1038/cddis.2014.373
DO - 10.1038/cddis.2014.373
M3 - Article
VL - 5
SP - 1
EP - 13
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
ER -