Fathi Ezzatollah, Montazersaheb Soheila, Sanaat Zohreh, Nakhlband Ailar, Vandghanooni Somayeh, Farahzadi Raheleh, Vietor Ilja
Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Curr Stem Cell Res Ther. 2023;18(2):231-236. doi: 10.2174/1574888X17666220511141123.
Increased oxygen species levels can induce mitochondrial DNA damage and chromosomal aberrations and cause defective stem cell differentiation, leading finally to senescence of stem cells. In recent years, several studies have reported that antioxidants can improve stem cell survival and subsequently affect the potency and differentiation of these cells. Finding factors, which reduce the senescence tendency of stem cells upon expansion, has great potential for cellular therapy in regenerative medicine. This study aimed to evaluate the effects of L-carnitine (LC) on the aging of C-kit+ hematopoietic progenitor cells (HPCs) via examining the expression of some signaling pathway components.
For this purpose, bone marrow resident C-kit+ HPCs were enriched by the magnetic-activated cell sorting (MACS) method and were characterized using flow cytometry as well as immunocytochemistry. Cells were treated with LC, and at the end of the treatment period, the cells were subjected to the realtime PCR technique along with a western blotting assay for measurement of the telomere length and assessment of protein expression, respectively.
The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the TERT protein expression. In addition, a significant increase was observed in the protein expression of p38, p53, BCL2, and p16 as key components of the telomere-dependent pathway.
It can be concluded that LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the C-kit+ HPCs via these signaling pathway components.
活性氧水平升高可诱导线粒体DNA损伤和染色体畸变，并导致干细胞分化缺陷，最终导致干细胞衰老。近年来，多项研究报道抗氧化剂可提高干细胞存活率，并随后影响这些细胞的潜能和分化。寻找能够降低干细胞在扩增过程中衰老倾向的因素，在再生医学的细胞治疗中具有巨大潜力。本研究旨在通过检测一些信号通路成分的表达，评估左旋肉碱（LC）对C-kit+造血祖细胞（HPCs）衰老的影响。
为此，通过磁珠激活细胞分选（MACS）方法富集骨髓驻留C-kit+HPCs，并使用流式细胞术以及免疫细胞化学进行鉴定。细胞用LC处理，在处理期结束时，分别对细胞进行实时PCR技术以及蛋白质印迹分析，以测量端粒长度和评估蛋白质表达。
结果表明，0.2 mM LC导致端粒长度延长，并增加了TERT蛋白表达。此外，作为端粒依赖性途径的关键成分，p38、p53、BCL2和p16的蛋白质表达显著增加。
可以得出结论，LC可作为增加细胞存活和维持C-kit+HPCs的有效因素，通过这些信号通路成分增加端粒长度。
