PMID- 28817667
OWN - NLM
STAT- MEDLINE
DCOM- 20171006
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 8
DP  - 2017
TI  - Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human 
      platelets.
PG  - e0182374
LID - 10.1371/journal.pone.0182374 [doi]
LID - e0182374
AB  - Thrombin-induced platelet activation requires substantial amounts of ATP. 
      However, the specific contribution of each ATP-generating pathway i.e., oxidative 
      phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms 
      involved in the thrombin-induced activation of energy metabolism remain unclear. 
      Here we report an integral analysis on the role of both energy pathways in human 
      platelets activated by several agonists, and the signal transducing mechanisms 
      associated with such activation. We found that thrombin, Trap-6, arachidonic 
      acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic 
      flux (3-38 times vs. non-activated platelets) whereas ristocetin was ineffective. 
      OxPhos (33 times) and mitochondrial transmembrane potential (88%) were increased 
      only by thrombin. OxPhos was the main source of ATP in thrombin-activated 
      platelets, whereas in platelets activated by any of the other agonists, 
      glycolysis was the principal ATP supplier. In order to establish the biochemical 
      mechanisms involved in the thrombin-induced OxPhos activation in platelets, 
      several signaling pathways associated with mitochondrial activation were 
      analyzed. Wortmannin and LY294002 (PI3K/Akt pathway inhibitors), ristocetin and 
      heparin (GPIb inhibitors) as well as resveratrol, ATP (calcium-release 
      inhibitors) and PP1 (Tyr-phosphorylation inhibitor) prevented the 
      thrombin-induced platelet activation. These results suggest that thrombin 
      activates OxPhos and glycolysis through GPIb-dependent signaling involving PI3K 
      and Akt activation, calcium mobilization and protein phosphorylation.
FAU - Corona de la Pena, Norma
AU  - Corona de la Pena N
AD  - Unidad de Investigacion en Trombosis, Hemostasia y Aterogenesis, Hospital Carlos 
      McGregor, Mexico City, Mexico.
FAU - Gutierrez-Aguilar, Manuel
AU  - Gutierrez-Aguilar M
AD  - Center for Human Nutrition, Washington University School of Medicine, St. Louis, 
      MO, United States of America.
FAU - Hernandez-Resendiz, Ileana
AU  - Hernandez-Resendiz I
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico City, 
      Mexico.
FAU - Marin-Hernandez, Alvaro
AU  - Marin-Hernandez A
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico City, 
      Mexico.
FAU - Rodriguez-Enriquez, Sara
AU  - Rodriguez-Enriquez S
AUID- ORCID: 0000-0002-0822-1233
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico City, 
      Mexico.
AD  - Laboratorio de Medicina Traslacional, Instituto Nacional de Cancerologia, Mexico 
      City, Mexico.
LA  - eng
PT  - Journal Article
DEP - 20170817
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Platelet Glycoprotein GPIb-IX Complex)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.21.5 (Thrombin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Blood Platelets/*metabolism
MH  - Calcium/metabolism
MH  - *Glycolysis
MH  - Humans
MH  - Mitochondria/metabolism
MH  - *Oxidative Phosphorylation
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Platelet Activation
MH  - Platelet Glycoprotein GPIb-IX Complex/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Thrombin/*metabolism
PMC - PMC5560607
COIS- Competing Interests: The authors have declared that no competing interest exist.
EDAT- 2017/08/18 06:00
MHDA- 2017/10/07 06:00
PMCR- 2017/08/17
CRDT- 2017/08/18 06:00
PHST- 2017/03/22 00:00 [received]
PHST- 2017/07/17 00:00 [accepted]
PHST- 2017/08/18 06:00 [entrez]
PHST- 2017/08/18 06:00 [pubmed]
PHST- 2017/10/07 06:00 [medline]
PHST- 2017/08/17 00:00 [pmc-release]
AID - PONE-D-17-11291 [pii]
AID - 10.1371/journal.pone.0182374 [doi]
PST - epublish
SO  - PLoS One. 2017 Aug 17;12(8):e0182374. doi: 10.1371/journal.pone.0182374. 
      eCollection 2017.