N6-methyideoxyadenosine, a nucleoside commonly found in prokaryotes, induces C2C12 myogenic differentiation
N6-methyideoxyadenosine, a nucleoside commonly found in prokaryotes, induces C2C12 myogenic differentiation
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DOI：
10.1016/j.bbrc.2003.12.132
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发表时间：
2004-02-06
影响因子：
3.1
通讯作者：
Wion, D
中科院分区：
文献类型：
--
作者：
Charles, MP;Ravanat, JL;Wion, D
N '-甲基-2'-脱氧腺苷（MedAdo）是天然存在于原核DNA中的核苷。有趣的是，DNA中腺嘌呤的N-6-甲基化似乎在进化过程中被逆选择，因为MedAdo至今尚未在哺乳动物DNA中被检测到。我们在这里表明，MedAdo治疗诱导C2Cl 2成肌细胞中的肌发生。使用基于HPLC偶联电喷雾电离串联质谱的方法研究C2Cl 2 DNA中MedAdo的存在，该方法比先前使用的测定法灵敏数千倍。通过这种方法，MedAdo在MedAdo处理的细胞的DNA中被检测到，但在对照细胞的DNA中仍然检测不到。此外，MedAdo调节p21、肌细胞生成素、mTOR和MHC的表达。有趣的是，在多能C2Cl 2细胞系中，MedAdo仅驱动向肌生成的分化。因此，MedAdo的生物学效应在BMP-2的存在下被抑制，BMP-2将C2Cl 2从肌源性谱系细胞转分化为成骨谱系细胞。总之，这些结果表明MedAdo是一种新的肌生成诱导剂，并进一步扩展了这种甲基化核苷的分化潜力。此外，这些数据提出了一种有趣的可能性，即MedAdo对细胞分化的生物学效应可能导致其在真核生物中的反选择。(C)2003年爱思唯尔公司All rights reserved.
N'-Methyl-2'-deoxyadenosine (MedAdo) is a nucleoside naturally found in prokaryotic DNA. Interestingly, the N-6-methylation of adenine in DNA seems to have been counter-selected during the course of evolution since MedAdo has not been detected in mammalian DNA until now. We show here that treatment with MedAdo induces myogenesis in C2Cl2 myoblasts. The presence of MedAdo in C2Cl2 DNA was investigated using a method based on HPLC coupled to electrospray ionization tandem mass spectrometry which is several thousand fold more sensitive than assays used previously. By this procedure, MedAdo is detected in the DNA from MedAdo-treated cells but remains undetectable in the DNA from control cells. Furthermore, MedAdo regulates the expression of p21, myogenin, mTOR, and MHC. Interestingly, in the pluripotent C2Cl2 cell line, MedAdo drives the differentiation towards myogenesis only. Thus, the biological effect of MedAdo is suppressed in the presence of BMP-2 which transdifferentiates C2Cl2 from myogenic into osteogenic lineage cells. Taken together these results point to MedAdo as a novel inducer of myogenesis and further extends the differentiation potentialities of this methylated nucleoside. Furthermore, these data raise the intriguing possibility that the biological effects of MedAdo on cell differentiation may have led to its counter-selection in eukaryotes. (C) 2003 Elsevier Inc. All rights reserved.