How platelets die
MSU scientists: to stop bleeding, platelet must "die"
MSU Press Service
A team of scientists led by physicists from Moscow University has discovered the mechanism of programmed cell death of platelets, as a result of which the process of blood clotting is accelerated by 1000 – 10000 times. The results of the study are published in the Journal of Thrombosis and Haemostasis (Obydennyy et al., Dynamics of calcium spiking, mitochondrial collapse and phosphatidylserine exposure in platelet subpopulations during activation).
Platelets are cells contained in the blood and are responsible for stopping bleeding: they learn about damage to a blood vessel and come together, creating strong aggregates and preventing blood loss. This process is called hemostasis (from Greek. haimatos – blood, stasis – stop). The ability to stick together and clog the damaged area of the vessel platelets are obtained as a result of the activation process. Scientists believe that the platelet is one of the simplest cells in the human body, and the task of his whole life is to decide whether to activate or not. But, despite the fact that it is already well known how platelets are arranged, there are still questions about the mechanisms of their functioning. The article, the lead author of which is Professor of the Department of Medical Physics of the Faculty of Physics of Moscow State University, Doctor of Physico-Mathematical Sciences Mikhail Panteleev, is devoted to how the process of platelet activation occurs.
There are two types of activated platelets in total: simple (aggregating) and overactivated (procoagulant).
On the left is an ordinary activated platelet (photo from a scanning electron microscope), on the right is an overactivated platelet (photo from a transmission electron microscope). Source: Mikhail Panteleev
When activated, simple aggregating platelets do not increase and take an amoeboid shape with many legs for better adhesion and can spread over the surface. Such platelets form the main body of the thrombus. And overactivated platelets become spherical when activated and increase several times (in English terminology, they are called "balloons" – "balloons"). They are able to strengthen the blood clot and accelerate blood clotting reactions. But the question remained: how do these cells divide into two types when activated? A team of scientists has figured out the most important mystery of platelet signaling.
It's all about the mitochondria. It is believed that mitochondria – organelles present in all animal (and plant) cells without exception, including platelets – provide them with energy due to redox reactions.
"But it seems that platelets need mitochondria not so much for energy, as for rapid suicide," Mikhail Panteleev begins the story.
Scientists were able to show how the cellular death of platelets (mitochondrial necrosis) triggers a chain of processes leading to the transition of platelets into an overactivated state. In other words, in order for a platelet to over-activate, it needs to die, because their purpose begins from the moment they "died". For this reason, platelets are also called "kamikaze cells".
"Previously, no one understood how a platelet makes a decision about which population to go to. We have deciphered the sequence of events: how signaling occurs in a platelet, and how this cell makes a decision about death," says Mikhail Panteleev.
The process of mitochondrial necrosis in detail. Two platelets are spread out on the substrate. Living mitochondria glow green, red is a marker for cell death. The platelet on the left dies as a result of mitochondrial collapse, and its neighbor on the right lives peacefully. Photos from a confocal microscope. Source: Mikhail Panteleev
Together with colleagues from the FNCC DGOI im. Dmitry Rogachev, the Center for Theoretical Problems of Physico-Chemical Pharmacology of the Russian Academy of Sciences and the Therapeutic Faculty of the N.I. Pirogov RNIMU, scientists found out that the activation process proceeds as follows. Platelet activators are many, but the main ones are: collagen, ADP and thrombil. The platelet receives different concentrations of the activator, and it responds to them with a different pulse frequency of calcium concentrations in the cytoplasm. This phenomenon is called calcium oscillations. Platelet mitochondria take and accumulate calcium in themselves, and when its concentration exceeds the critical mark, the process of mitochondrial necrosis (cell death) of platelets is triggered: calcium and reactive oxygen species splash out of the mitochondria, the cytoskeleton of the cell is destroyed, and the platelet greatly increases in volume. As a result, the lipid phosphatidylserine appears on the outer membrane of the spherical platelet, which has increased in size, and is responsible for rapid blood clotting. And all this happens at lightning speed.
Last year, the same group of researchers published an article in the journal Molecular BioSystems on the theoretical mechanism of mitochondrial necrosis, in this paper this process was experimentally proven.
Moreover, another article by Mikhail Panteleev and his colleagues ("Systems biology insights into the meaning of the platelet's dual-receptor thrombin singalling") from the Faculty of Physics and the Faculty of Fundamental Medicine of Moscow State University has been accepted for publication. Scientists explain an interesting mystery of the device of intracellular signaling of platelets: for the first time it was shown that the same activator has two receptors in a platelet to achieve maximum sensitivity.
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