Journal article
Regulatory Role of Proteasome in Determination of Platelet Life Span
The Journal of biological chemistry, Vol.288(10), pp.6826-6834
03/08/2013
DOI: 10.1074/jbc.M112.403154
PMCID: PMC3591593
PMID: 23329846
Abstract
Limit of platelet life span (8-10 days) is determined by the activity of a putative "internal clock" composed of Bcl-2 family proteins, whereas the role of other molecular players in this process remains obscure. Here, we sought to establish a central role of proteasome in platelet life span regulation. Administration of mice with inhibitors of proteasome peptidase activity induced significant thrombocytopenia. This was associated with enhanced clearance of biotin-labeled platelets from circulation and reduction in average platelet half-life from 66 to 37 h. Cells pretreated in vitro with proteasome inhibitors exhibited augmented annexin V binding and a drop in mitochondrial transmembrane potential indicative of apoptotic cell death and decreased platelet life span. These cells were preferentially phagocytosed by monocyte-derived macrophages, thus linking proteasome activity with platelet survival. The decisive role of proteasome in this process was underscored from enhanced expression of conformationally active Bax in platelets with attenuated proteasome activity, which was consistent with proapoptotic phenotype of these cells. The present study establishes a critical role of proteasome in delimiting platelet life span ostensibly through constitutive elimination of the conformationally active Bax. These findings bear potential implications in clinical settings where proteasome peptidase activities are therapeutically targeted.
Details
- Title: Subtitle
- Regulatory Role of Proteasome in Determination of Platelet Life Span
- Creators
- Manasa K. Nayak - Banaras Hindu UniversityParesh P. Kulkarni - Banaras Hindu UniversityDebabrata Dash - Banaras Hindu University
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.288(10), pp.6826-6834
- DOI
- 10.1074/jbc.M112.403154
- PMID
- 23329846
- PMCID
- PMC3591593
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 9
- Grant note
- Department of Biotechnology Council of Scientific and Industrial Research; Council of Scientific & Industrial Research (CSIR) - India Department of Science and Technology, Government of India; Department of Science & Technology (India)
- Language
- English
- Date published
- 03/08/2013
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359894002771
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