Sirtuins are evolutionarily conserved NAD+-dependent acetyl-lysine deacetylases that belong to class III type of histone deacetylases. In humans, seven sirtuin isoforms (Sirt1 to Sirt7) have been identified. Sirtinol, a cell permeable lactone ring derived from naphthol, is a dual Sirt1/Sirt2 inhibitor of low potency whereas EX-527 is a potent and selective Sirt1 inhibitor. Here we have demonstrated that Sirt1, Sirt2 and Sirt3 are expressed in enucleate platelets. Both sirtinol or EX-527 induced apoptosis-like changes in platelets as revealed from enhanced annexin V binding, ROS production and drop in mitochondrial transmembrane potential. Above changes were associated with increased phagocytic clearance of the platelets by macrophages. Expression of acetylated p53 and the conformationally active form of Bax were found to be significantly higher in both sirtinol- as well as EX-527-treated platelets, thus implicating p53-Bax axis in apoptosis induced by sirtuin inhibitors. Administration of either sirtinol or EX-527 in mice led to reduction in both platelet count and number of reticulated platelets. Our results, for the first time, implicate sirtuins as a central player in determination of platelet aging. Since sirtuin inhibitors are being evaluated for their anti-tumor activity, this study rekindles attention to potential side effect of sirtuin inhibition in delimiting platelet life span and management of thrombosis.
Pharmacology, Toxicology and Pharmaceutical Science
2
5%
Neuroscience
2
5%
Other
2
5%
Unknown
9
21%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 February 2018.
All research outputs
#7,432,872
of 34,089,221 outputs
Outputs from Journal of Biological Chemistry
#7,640
of 29,676 outputs
Outputs of similar age
#74,100
of 307,003 outputs
Outputs of similar age from Journal of Biological Chemistry
#121
of 480 outputs
Altmetric has tracked 34,089,221 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 29,676 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one has gotten more attention than average, scoring higher than 67% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 307,003 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 480 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
