Department of Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University New Orleans, LA 70112, USA.
Toxicol Appl Pharmacol. 2010 May 1;244(3):263-72. doi: 10.1016/j.taap.2010.01.001. Epub 2010 Jan 18.
Environmental exposure to arsenic is an important public health issue. The effects of arsenic on different tissues and organs have been intensively studied. However, the effects of arsenic on bone marrow mesenchymal stem cells (MSCs) have not been reported. This study is designed to investigate the cell death process caused by arsenite and its related underlying mechanisms on MSCs. The rationale is that absorbed arsenic in the blood circulation can reach to the bone marrow and may affect the cell survival of MSCs.
MSCs of passage 1 were purchased from Tulane University, grown till 70% confluency level and plated according to the experimental requirements followed by treatment with arsenite at various concentrations and time points. Arsenite (iAs(III)) induced cytotoxic effects were confirmed by cell viability and cell cycle analysis. For the presence of canonic apoptosis markers; DNA damage, exposure of intramembrane phosphotidylserine, protein and m-RNA expression levels were analyzed.
iAs(III) induced growth inhibition, G2-M arrest and apoptotic cell death in MSCs, the apoptosis induced by iAs(III) in the cultured MSCs was, via altering Bcl-2 family proteins and by involving intrinsic pathway.
iAs(III) can induce apoptosis in bone marrow-derived MSCs via Bcl-2 family proteins, regulating intrinsic apoptotic pathway. Due to the multipotency of MSC, acting as progenitor cells for a variety of connective tissues including bone, adipose, cartilage and muscle, these effects of arsenic may be important in assessing the health risk of the arsenic compounds and understanding the mechanisms of arsenic-induced harmful effects.
环境砷暴露是一个重要的公共卫生问题。砷对不同组织和器官的影响已得到深入研究。然而，砷对骨髓间充质干细胞（MSCs）的影响尚未报道。本研究旨在探讨亚砷酸盐引起的细胞死亡过程及其在 MSCs 中的相关潜在机制。其基本原理是，血液循环中吸收的砷可以到达骨髓，并可能影响 MSCs 的细胞存活。
本研究从 Tulane 大学购买传代 1 代的 MSCs，培养至 70%汇合度，并根据实验要求进行铺板，然后用不同浓度和时间点的亚砷酸盐进行处理。通过细胞活力和细胞周期分析来验证亚砷酸盐（iAs(III)）诱导的细胞毒性作用。为了检测到典型的凋亡标志物，分析了 DNA 损伤、膜磷酯酰丝氨酸暴露、蛋白和 m-RNA 表达水平。
iAs(III)诱导 MSCs 生长抑制、G2-M 期阻滞和凋亡性细胞死亡，iAs(III)诱导培养的 MSCs 凋亡是通过改变 Bcl-2 家族蛋白并涉及内在途径实现的。
iAs(III)可以通过 Bcl-2 家族蛋白诱导骨髓来源的 MSCs 凋亡，调节内在凋亡途径。由于 MSC 的多能性，作为包括骨、脂肪、软骨和肌肉在内的多种结缔组织的祖细胞，这些砷化合物的影响可能在评估砷化合物的健康风险和理解砷诱导的有害影响的机制方面非常重要。
