Iqbal Hana'a, Naeem Nadia, Haneef Kanwal, Salim Asmat
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Dow University of Health Sciences, Karachi, Pakistan.
Mol Biol Rep. 2023 May;50(5):4119-4131. doi: 10.1007/s11033-023-08321-8. Epub 2023 Mar 6.
With advancing age of stem cells, dysregulation of various processes at the cellular level occurs, thereby decreasing their regeneration potential. One of the changes that occurs during the aging process is the accumulation of reactive oxygen species (ROS), which accelerates the processes of cellular senescence and cell death. The aim of this study is to evaluate two antioxidant compounds; Chromotrope 2B and Sulfasalazine, for their antioxidant effects on young and old rat bone marrow mesenchymal stem cells (MSCs).
Oxidative stress was induced in MSCs by 5 µM dexamethasone for 96 h and the cells were treated with Chromotrope 2B or Sulfasalazine, 50 µM each. The effects of antioxidant treatment following oxidative stress induction was evaluated by transcriptional profiling of genes involved in the oxidative stress and telomere maintenance. Expression levels of Cat, Gpx7, Sod1, Dhcr24, Idh1, and Txnrd2 were found to be increased in young MSCs (yMSCs) as a result of oxidative stress, while Duox2, Parp1, and Tert1 expression were found to be decreased as compared to the control. In old MSCs (oMSCs), the expressions of Dhcr24, Txnrd2, and Parp1 increased, while that of Duox2, Gpx7, Idh1, and Sod1 decreased following oxidative stress. In both MSC groups, Chromotrope 2B prompted decrease in the ROS generation before and after the induction of oxidative stress. In oMSCs, ROS content was significantly reduced in the Sulfasalazine treated group.
Our findings suggest that both Chromotrope 2B and Sulfasalazine possess the potential to reduce the ROS content in both age groups, though the latter was found to be more potent. These compounds can be used to precondition MSCs to enhance their regenerative potential for future cell-based therapeutics.
随着干细胞年龄的增长，细胞水平上各种过程会出现失调，从而降低其再生潜力。衰老过程中发生的变化之一是活性氧（ROS）的积累，这加速了细胞衰老和细胞死亡过程。本研究的目的是评估两种抗氧化化合物；铬变素2B和柳氮磺胺吡啶，对年轻和老年大鼠骨髓间充质干细胞（MSC）的抗氧化作用。
用5μM地塞米松诱导MSC氧化应激96小时，并用铬变素2B或柳氮磺胺吡啶（各50μM）处理细胞。通过对参与氧化应激和端粒维持的基因进行转录谱分析，评估氧化应激诱导后抗氧化处理的效果。发现氧化应激导致年轻MSC（yMSC）中Cat、Gpx7、Sod1、Dhcr24、Idh1和Txnrd2的表达水平升高，而与对照组相比，Duox2、Parp1和Tert1的表达降低。在老年MSC（oMSC）中，氧化应激后Dhcr24、Txnrd2和Parp1的表达增加，而Duox2、Gpx7、Idh1和Sod1的表达降低。在两个MSC组中，铬变素2B促使氧化应激诱导前后ROS生成减少。在oMSC中，柳氮磺胺吡啶处理组的ROS含量显著降低。
我们的研究结果表明，铬变素2B和柳氮磺胺吡啶都具有降低两个年龄组ROS含量的潜力，尽管发现后者更有效。这些化合物可用于预处理MSC，以增强其在未来基于细胞的治疗中的再生潜力。
