Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

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.

Catalase Inhibits Ionizing Radiation-Induced Apoptosis in Hematopoietic Stem and Progenitor Cells

“…Previous studies, including those from our laboratory, indicated that acute BM radiation injury is, at least in part, attributable to the induction of apoptosis in HSPCs [3,6,18], suggesting that inhibition of IR-induced apoptosis may be an effective approach to protecting BM radiation injury. CAT is an extremely potent antioxidant We and others have demonstrated that IR-induced ROS play a critical role in radiation tissue injury [10][11][12][18][19][20]. IR induces ROS production in irradiated cells as a consequence of radiolysis of water, which can cause DNA damage, ultimately leading to apoptosis and/or cellular senescence.…”

“…It has been shown that IR-induced DNA damage significantly contributes to radiation toxicity [10,15,18]. However, it has not been determined whether CAT treatment has any effects on IR-induced DNA damage in HSPCs.…”

“…If the accumulation of ROS exceeds the capacity of the antioxidant system, oxidative stress can cause DNA damage, leading to apoptosis and/or cellular senescence [3,6,10,[14][15][16]. Given the significant involvement of ROS in IR-induced cell killing and normal tissue damage, it has been proposed that the use of certain antioxidants might be helpful for the prevention of radiation toxicity [10,12,17,18].…”

X-ray radiation effect of C-arm on adipose tissue-mesenchymal stem cell viability and population doubling time

“…DNA is the most important target macromolecule in cell injury and death. 21 Free radicals may enter the cell by diffusion through cell membrane and thereby damaging cell macromolecules, particularly DNA. Cell endurance to irradiation is affected by the ability to produce antioxidants and the ability to repair DNA damage.…”

The universal non-neuronal nature of Parkinson's disease: A theory

“…In vitro research has shown that exposure to H 2 O 2 can lead to chromosomal translocations in HSCs 61 . Ionizing radiation is also known to affect HSCs, as it has been found to promote differentiation, short-term apoptosis and long-term senescence of HSCs 62 . Work with Drosophila supports the role of ROS in the regulation of hematopoietic cell fate.…”