FIG. 2.
The signal pathways involved in ROS regulation in hematopoietic stem cells (HSCs). The activation of ataxia telangiectasia mutated (ATM) kinase, phosphoinositide 3-kinase (PI3K)/Akt, phosphorylates FoxO transcription factor 3 (FoxO3a), phosphatase and tensin homolog (PTEN), p53, PR domain-containing 16 (Prdm16), hypoxia inducible factor (HIF)-1α, p38 mitogen-activated protein kinase (MAPK), and nuclear factor erythroid-2-related factor 2 (Nrf2) negatively regulate ROS by up-regulating the antioxidant enzymes. PTEN can indirectly decrease ROS by negatively regulating the PI3K/Akt/mammalian target of rapamycin (mTOR), which can up-regulate the ROS levels. The increased ROS level can activate the p38MAPK, which can elevate the expression of the tumor suppressors p16Ink4a and p19Arf, resulting in HSC compartment loss. (To see this illustration in color the reader is referred to the web version of this article at www.liebertonline.com/ars).