Abstract Number: PB1656
Meeting: ISTH 2020 Congress
Background: Deamidation is commonly viewed as a post-translational modification that sets an expiration date on proteins. This spontaneous reaction accounts for the erosion, with time, of Asn residues within proteins, that are converted to Asp/IsoAsp residues. Such changes entail structural and functional alterations. Among apoptosis regulators of the Bcl-2 family, Bcl‑xL shows the unique characteristic to be either singly or doubly deamidated. We developed tools to highlight the sequential deamidation reactions targeting Asn52 first, and later Asn66 in the protein. While monodeamidation provides Bcl‑xL with a gain of autophagic activity, double deamidation impairs Bcl‑xL anti-apoptotic functions. One of the unique traits of platelets is to rely on the balance between anti-apoptotic Bcl‑xL and pro-apoptotic Bak for their survival in circulation at steady state. How Bcl‑xL is regulated to terminate platelet life is currently unknown.
Aims: As Bcl‑xL regulates the life span of platelets and proplatelet-forming megakaryocytes, we aimed to investigate the status of Bcl-xL deamidation among young and old platelets.
Methods: We therefore analyzed Bcl-xL deamidation state in platelets from mice models where platelets lifespan was manipulated. In parallel, we compared human platelets obtained at steady state from healthy controls, to platelets newly synthesized after recovery from acute thrombocytopenia
Results: We found that while expression levels of Asn52 monodeamidated Bcl‑xL remains unchanged, Asn52Asn66 doubly-deamidated Bcl‑xL is virtually absent in young platelets and accumulates in old platelets.
Conclusions: Bcl-xL deamidation status therefore fulfills all the criteria of a bona fide aging marker of platelets. Ongoing work addresses whether Bcl-xL deamidation is responsible for platelets death, and whether it can be instrumental in the detection of hematologic malignancies.
To cite this abstract in AMA style:James C, Bobo C, Ganatirkar P, Uren R, Riviere E, Josefsson E, Kluck R, Priault M. Bcl-Xl Deamidation State Tells Platelets Age [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/bcl-xl-deamidation-state-tells-platelets-age/. Accessed May 18, 2021.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/bcl-xl-deamidation-state-tells-platelets-age/