Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12 myotubes
Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12 myotubes
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DOI：
10.1007/s13105-017-0578-9
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发表时间：
2017-07
影响因子：
3.4
通讯作者：
N. Takahashi;A. Kimura;S. Naito;Mika Yoshida;O. Kumano;Takeshi Suzuki;Satoshi Itaya;M. Moriya;M. Tsuji;M. Ieko
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文献类型：
--
作者：
N. Takahashi;A. Kimura;S. Naito;Mika Yoshida;O. Kumano;Takeshi Suzuki;Satoshi Itaya;M. Moriya;M. Tsuji;M. Ieko
肌磷脂是一种跨膜蛋白，表达于大型动物骨骼肌和心房肌的肌/内质网。Sarcolipin通过调节sarco/内质网Ca2+ atp酶的功能，在产热中起着至关重要的作用，从而参与产热和全身代谢。在骨骼肌中，内质网（ER）应激与胰岛素抵抗、肌肉疾病和低/过度收缩等多种疾病有关。在这里，我们研究了内质网应激对骨骼肌细胞C2C12肌管中肌磷脂表达的影响。首先，在肌形成过程中证实了肌磷脂的基因表达。然后用tunicamycin或thapsigarin诱导C2C12肌管内质网应激。内质网应激诱导显著降低了肌磷脂信使RNA （mRNA）和蛋白的表达。用IRE1抑制剂4μ8C处理后发现，IRE1可被内质网胁迫激活，并具有强大的内切酶活性。另一方面，放线菌素d处理降低了内质网应激下肌磷脂mRNA的稳定性。综上所述，内质网应激通过改变C2C12肌管中肌磷脂mRNA的稳定性来抑制肌磷脂的表达。
Sarcolipin is a transmembrane protein expressed in the sarco/endoplasmic reticulum of skeletal and atrial muscles in large animals. Sarcolipin plays crucial roles in heat production through modifying the function of sarco/endoplasmic reticulum Ca2+ATPase, thereby being involved in thermogenesis and systemic metabolism. In skeletal muscle, endoplasmic reticulum (ER) stress has been implicated in several conditions, such as insulin resistance, muscle diseases, and hypo/hyper-contraction. Here, we investigated the effect of ER stress on sarcolipin expression in skeletal muscle cells, C2C12 myotubes. First, gene expression of sarcolipin was confirmed in the cells during myogenesis. Then, ER stress was induced in C2C12 myotubes by treatment with tunicamycin or thapsigargin. Sarcolipin messenger RNA (mRNA) and protein expression were significantly reduced by ER stress induction. The reduction was independent of inositol-requiring element 1 (IRE1), which is activated by ER stress and has potent endonuclease activity, when evaluated by treatment with an IRE1 inhibitor, 4μ8C. On the other hand, sarcolipin mRNA stability was reduced under the ER stress when evaluated by treatment with actinomycin D. In conclusion, these results show that ER stress represses sarcolipin expression due to changes in mRNA stability in C2C12 myotubes.