Garcia-Souza 2013 Abstract IOC80
Garcia-Souza LF (2013) Thrombin trigger mitochondrial functional remodeling in human platelets. Mitochondr Physiol Network 18.09. |
Link: IOC80 Schroecken
Garcia-Souza Luiz F, Hottz ED, Morton KA, Santiago APSA, Bozza FA, Oliveira MF (2013)
Event: MiPNet18.09 IOC80
Introduction: Evidence has indicated that pro-coagulant factors modulate platelet energy and redox metabolism pathways. However, the involvement of mitochondria during platelet activation remain poorly understood and was investigated in the present work.
Materials and methods: Human platelets were collected from healthy volunteers, isolated in M199 medium, and subsequently challenged with different thrombin concentrations. Several parameters were analyzed in activated platelets such as P-selectin externalization, respiration, lactate and nitric oxide (NO) production. The assessment of oxygen flow and metabolic states in platelets was carried out in the presence of several mitochondrial modulators by titrating each one of them in the following order: Oligomycin, FCCP, rotenone and Antimycin A in the presence or absence of thrombin.
Results and discussion: During platelet activation, CD62p expression increased and was followed by an increase in lactate secretion and NO production with high correlation between each other. Analyzing mitochondrial states we could detect changes in several states, mainly ROUTINE, OXPHOS, proton leak and reserve capacity. However, normalizing our signal by the highest uncoupled oxygen consumption (ET-pathway), we detected differences in residual oxygen consumption (ROX) alongside other states.
Conclusions: Our data indicate that mitochondria from human platelets are affected by their ativation. This raises the concern of using platelets as models of indirect studies such as mitochondrial diseases and Alzheimer. The mitochondria play a very important role in platelet physiology and is not an inert within the cell, is affected by a number of substances that are present at the time of activation, such as calcium and nitric oxide. Therefore, it is necessary to evaluate the changes in mitochondrial human platelets against different agonists and inhibitors of coagulation.
β’ Keywords: Platelet, Thrombin, Activation
β’ O2k-Network Lab: BR Rio de Janeiro Oliveira MF
Labels: MiParea: Respiration
Organism: Human
Tissue;cell: Blood cells
Preparation: Intact cells
Enzyme: Complex I
Coupling state: LEAK, ROUTINE, ET
HRR: Oxygraph-2k