Hematopoietic Stem Cell Injury Induced by Ionizing Radiation
Publication: Antioxidants & Redox Signaling
Volume 20, Issue Number 9
Abstract
Significance: Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Recent Advances: Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Critical Issues: Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. Future Directions: In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression. Antioxid. Redox Signal. 20, 1447–1462.
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Published In
Antioxidants & Redox Signaling
Volume 20 • Issue Number 9 • March 20, 2014
Pages: 1447 - 1462
PubMed: 24124731
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Copyright 2014, Mary Ann Liebert, Inc.
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Published in print: March 20, 2014
Published online: 27 February 2014
Published ahead of print: 10 February 2014
Published ahead of production: 14 October 2013
Accepted: 13 October 2013
Received: 2 October 2013
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