Javazon Elisabeth H, Radhi Mohamed, Gangadharan Bagirath, Perry Jennifer, Archer David R
Department of Biology, Morehouse College, 830 Westview Drive Southwest, Atlanta, GA 30314-3773, USA.
Anemia. 2012;2012:387385. doi: 10.1155/2012/387385. Epub 2012 Jun 4.
Previous studies have shown that the sickle environment is highly enriched for reactive oxygen species (ROS). We examined the oxidative effects of sickle cell disease on hematopoietic stem cell function in a sickle mouse model. In vitro colony-forming assays showed a significant decrease in progenitor colony formation derived from sickle compared to control bone marrow (BM). Sickle BM possessed a significant decrease in the KSL (c-kit(+), Sca-(1+), Lineage(-)) progenitor population, and cell cycle analysis showed that there were fewer KSL cells in the G(0) phase of the cell cycle compared to controls. We found a significant increase in both lipid peroxidation and ROS in sickle-derived KSL cells. In vivo analysis demonstrated that normal bone marrow cells engraft with increased frequency into sickle mice compared to control mice. Hematopoietic progenitor cells derived from sickle mice, however, demonstrated significant impairment in engraftment potential. We observed partial restoration of engraftment by n-acetyl cysteine (NAC) treatment of KSL cells prior to transplantation. Increased intracellular ROS and lipid peroxidation combined with improvement in engraftment following NAC treatment suggests that an altered redox environment in sickle mice affects hematopoietic progenitor and stem cell function.
先前的研究表明，镰状环境中活性氧（ROS）高度富集。我们在镰状小鼠模型中研究了镰状细胞病对造血干细胞功能的氧化作用。体外集落形成试验显示，与对照骨髓（BM）相比，镰状来源的祖细胞集落形成显著减少。镰状骨髓中KSL（c-kit(+)、Sca-(1+)、谱系(-)）祖细胞群体显著减少，细胞周期分析表明，与对照相比，处于细胞周期G(0)期的KSL细胞更少。我们发现镰状来源的KSL细胞中脂质过氧化和ROS均显著增加。体内分析表明，与对照小鼠相比，正常骨髓细胞植入镰状小鼠的频率增加。然而，来自镰状小鼠的造血祖细胞在植入潜力方面表现出显著受损。我们观察到在移植前用N-乙酰半胱氨酸（NAC）处理KSL细胞可部分恢复植入。NAC处理后细胞内ROS和脂质过氧化增加以及植入改善表明，镰状小鼠中氧化还原环境的改变影响造血祖细胞和干细胞功能。
