PMID:25603016

Citation	'Xiao, X, Luo, H, Vanek, KN, LaRue, AC, Schulte, BA and Wang, GY (2015) Catalase Inhibits Ionizing Radiation-Induced Apoptosis in Hematopoietic Stem and Progenitor Cells. Stem Cells Dev. '
Abstract	Hematologic toxicity is a major cause of mortality in radiation emergency scenarios and a primary side effect concern in patients undergoing chemo-radiotherapy. Therefore, there is a critical need for the development of novel and more effective approaches to manage this side effect. Catalase is a potent antioxidant enzyme, that coverts hydrogen peroxide into hydrogen and water. In the present study, we evaluated the efficacy of catalase as a protectant against ionizing radiation (IR)-induced toxicity in hematopoietic stem and progenitor cells (HSPCs). The results revealed that catalase treatment markedly inhibits IR-induced apoptosis in murine hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Subsequent colony-forming cell and cobble-stone area forming cell assays showed that catalase-treated HSPCs can not only survive irradiation-induced apoptosis, but also have higher clonogenic capacity, compared with vehicle-treated cells. Moreover, transplantation of catalase-treated irradiated HSPCs results in high levels of multi-lineage and long-term engraftments whereas vehicle-treated irradiated HSPCs exhibit very limited hematopoiesis reconstituting capacity. Mechanistically, catalase treatment attenuates IR-induced DNA double-strand breaks and inhibits reactive oxygen species. Unexpectedly, we found that the radioprotective effect of catalase is associated with activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway and pharmacological inhibition of STAT3 abolishes the protective activity of catalase, suggesting that catalase may protect HSPCs against IR-induced toxicity via promoting STAT3 activation. Collectively, these results demonstrate a previously unrecognized mechanism whereby catalase inhibits IR-induced DNA damage and apoptosis in HSPCs.
Links	PubMed Online version:10.1089/scd.2014.0402
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HELPX:I2DFD6	Contributes to	GO:0004096: catalase activity	ECO:0000314:		F		Inhibits ionizing radiation induced apoptosis in hematopoetic stem and progenitor cells	complete CACAO 10560

References

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