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The majority of hematopoietic stem cells (HSCs) are maintained in a quiescent state to minimize premature exhaustion induced by various stresses. However, quiescent HSCs are vulnerable to mutagenesis because of attenuated DNA repair and DNA damage response programs. Basal abundant expression of prosurvival BCL-2 proteins further endows HSCs with high resistance to apoptosis. In contrast, HSCs elicit strong activation of p53 upon DNA damage, resulting in enhanced activation of proapoptotic BCL-2 signals through p53. ASPP1, an apoptosis-stimulating protein of p53, is highly expressed in HSCs and preserves HSC pool integrity via selective induction of apoptosis. In this paper, we discuss the role of p53 and mitochondrial apoptosis in HSC regulation and introduce the current understanding of how p53 activity is regulated to achieve a good balance between maintaining the HSC pool and preventing hematological malignancies. [ABSTRACT FROM AUTHOR]

Aminoguanidine (AG), a prototype therapeutic dicarbonyl scavenger, is the most potent drug available today to inhibit the formation of advanced glycation endproducts (AGEs) and to reverse glycation-mediated damage in normal aging. This paper examines the ability of AG to cause damage to supercoiled plasmid DNA in the presence of the transition metal, Fe+3. Damage to DNA was dependent on the concentrations of both the transition metal and AG. We could detect hydroxyl radical as well as hydrogen peroxide during the incubation of AG with Fe+3. Thus this finding further cautions against the indiscriminate use of AG in clinical prophylaxis in diabetes and questions its use as a therapeutic agent. [ABSTRACT FROM AUTHOR]