Enzymes behind platelet death nailed
doi:10.1038/nindia.2015.75 Published online 1 June 2015
Researchers trying to solve the mystery behind the death of platelets — tiny cells responsible for blood coagulation — have found that a family of enzymes called sirtuins are responsible for their life1.
Blood platelets have a life span of 10-12 days, at the end of which they undergo programmed cell death or apoptosis and the cells are eaten up by macrophages. Decrease in platelet numbers (thombocytopenia) can lead to a bleeding tendency, which can often be fatal.
The researchers set out to study what limits platelet life span, how a young platelet turns old and why apoptosis happens in the end. They studied the signaling molecules that constitute the 'internal timer' of platelets and identified the signaling path involved.
"From biochemical studies on human blood as well as in mouse we found that the sirtuin family of deacetylases is responsible for preventing platelet death," says lead researcher Debabrata Dash from the Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University.
Sirtuins remove acetate groups from their target acetylated proteins. One of these targets is p53, known to cause cell apoptosis. Once p53 is deacetylated by sirtuins, the protein is destabilised and degraded by the proteasome system. When p53 level drops, the platelets live longer. The researchers found that platelets expressed sirutins — when sirtuins were inhibited, p53 became stable leading to cell death and thrombocytopenia.
The research implicates sirtuins as a central player in determination of platelet ageing. Sirtuin may, therefore, be a potential therapeutic target to induce apoptosis-like events in platelets and to reduce the severity of thrombosis or thrombocytosis, the researchers say.
1. Kunari, S. et al. Sirtuin inhibition induces apoptosis-like changes in platelets and thrombocytopenia. J. Biol. Chem. 290, 12290–12299 (2015)