Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets.
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 remai...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5560607?pdf=render |
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| author | Norma Corona de la Peña Manuel Gutiérrez-Aguilar Ileana Hernández-Reséndiz Álvaro Marín-Hernández Sara Rodríguez-Enríquez |
| author_facet | Norma Corona de la Peña Manuel Gutiérrez-Aguilar Ileana Hernández-Reséndiz Álvaro Marín-Hernández Sara Rodríguez-Enríquez |
| author_sort | Norma Corona de la Peña |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T00:18:40Z |
| format | Article |
| id | doaj.art-06057ad45b704e5bb9a1ead077b270a8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T00:18:40Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-06057ad45b704e5bb9a1ead077b270a82022-12-22T03:55:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018237410.1371/journal.pone.0182374Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets.Norma Corona de la PeñaManuel Gutiérrez-AguilarIleana Hernández-ReséndizÁlvaro Marín-HernándezSara Rodríguez-EnríquezThrombin-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.http://europepmc.org/articles/PMC5560607?pdf=render |
| spellingShingle | Norma Corona de la Peña Manuel Gutiérrez-Aguilar Ileana Hernández-Reséndiz Álvaro Marín-Hernández Sara Rodríguez-Enríquez Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets. PLoS ONE |
| title | Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets. |
| title_full | Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets. |
| title_fullStr | Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets. |
| title_full_unstemmed | Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets. |
| title_short | Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets. |
| title_sort | glycoprotein ib activation by thrombin stimulates the energy metabolism in human platelets |
| url | http://europepmc.org/articles/PMC5560607?pdf=render |
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