Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubes.
Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubes.
复制标题
DOI：
10.1002/jcb.21833
复制
发表时间：
2008-10-01
影响因子：
4
通讯作者：
Hasselgren, Per-Olof
中科院分区：
文献类型：
--
作者：
Menconi, Michael;Gonnella, Patricia;Petkova, Victoria;Lecker, Stewart;Hasselgren, Per-Olof
地塞米松处理的L 6（大鼠细胞系）和C2 C12（小鼠细胞系）肌管经常用作肌肉萎缩的体外模型。我们比较了不同浓度的地塞米松和皮质酮（啮齿动物中天然存在的糖皮质激素）对两种细胞系中蛋白质分解率、肌管大小和atrogin-1和MuRF 1 mRNA水平的影响。此外，糖皮质激素受体（GR）的表达及其在糖皮质激素诱导的代谢变化中的作用进行了测定。用地塞米松或皮质酮治疗导致L 6和C2 C12肌管中蛋白质降解速率的剂量依赖性增加，伴随着肌管直径减小25-30%。相同的处理增加了L 6和C2 C12肌管中的atrogin-1 mRNA水平，但令人惊讶的是，仅上调了L 6肌管中MuRF 1的表达。这两种细胞类型的GR和治疗与地塞米松或皮质酮下调总细胞GR水平，同时增加核转位的GR在L 6和C2 C12肌管。GR拮抗剂RU 38486抑制地塞米松和皮质酮诱导的atrogin-1和MuRF 1在L 6肌管中表达的增加，但不抑制C2 C12肌管中的表达。有趣的是，RU 38486在C2 C12中发挥激动剂作用，但在L 6肌管中没有。目前的结果表明，肌肉萎缩相关的反应地塞米松和皮质酮是相似的，但不相同，在L 6和C2 C12肌管。最值得注意的是，糖皮质激素对MuRF 1的调节和GR的作用在两种细胞系中可能是不同的。在将来的研究中使用培养的肌管以进一步探索肌肉萎缩的机制时，需要考虑这些差异。
Dexamethasone-treated L6 (a rat cell line) and C2C12 (a mouse cell line) myotubes are frequently used as in vitro models of muscle wasting. We compared the effects of different concentrations of dexamethasone and corticosterone (the naturally occurring glucocorticoid in rodents) on protein breakdown rates, myotube size, and atrogin-1 and MuRF1 mRNA levels in the two cell lines. In addition, the expression of the glucocorticoid receptor (GR) and its role in glucocorticoid-induced metabolic changes were determined. Treatment with dexamethasone or corticosterone resulted in dose-dependent increases in protein degradation rates in both L6 and C2C12 myotubes accompanied by 25-30% reduction of myotube diameter. The same treatments increased atrogin-1 mRNA levels in L6 and C2C12 myotubes but, surprisingly, upregulated the expression of MuRF1 in L6 myotubes only. Both cell types expressed the GR and treatment with dexamethasone or corticosterone downregulated total cellular GR levels while increasing nuclear translocation of the GR in both L6 and C2C12 myotubes. The GR antagonist RU38486 inhibited the dexamethasone- and corticosterone-induced increases in atrogin-1 and MuRF1 expression in L6 myotubes but not in C2C12 myotubes. Interestingly, RU38486 exerted agonist effects in the C2C12, but not in the L6 myotubes. The present results suggest that muscle wasting-related responses to dexamethasone and corticosterone are similar, but not identical, in L6 and C2C12 myotubes. Most notably, the regulation by glucocorticoids of MuRF1 and the role of the GR may be different in the two cell lines. These differences need to be taken into account when cultured myotubes are used in future studies to further explore mechanisms of muscle wasting.
登录
查看更多内容
影响因子：
2.7
作者：
Borski, RJ;Hyde, GN;Fruchtman, S
通讯作者：
Fruchtman, S
影响因子：
4.8
作者：
Du, J;Mitch, WE;Price, SR
通讯作者：
Price, SR
DOI：
10.1016/j.biocel.2005.06.002
发表时间：
2005-10-01
影响因子：
4
作者：
Evenson, AR;Fareed, MU;Hasselgren, PO
通讯作者：
Hasselgren, PO
影响因子：
6
作者：
Faggioni, R;Moser, A;Grunfeld, C
通讯作者：
Grunfeld, C
影响因子：
8.2
作者：
Heitzer, Marjet D.;Wolf, Irene M.;DeFranco, Donald B.
通讯作者：
DeFranco, Donald B.