Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12 myotubes

• Published in: Journal of physiology and biochemistry Vol. 73; no. 4; pp. 531 - 538
• Main Authors: Takahashi, Nobuhiko, Kimura, Atsushi P., Naito, Sumiyoshi, Yoshida, Mika, Kumano, Osamu, Suzuki, Takeshi, Itaya, Satoshi, Moriya, Mitsuru, Tsuji, Masahiro, Ieko, Masahiro
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-11-2017; Springer Nature B.V
• Subjects: Actinomycin; Adenosine triphosphatase; Animal Physiology; Animals; Biomedical and Life Sciences; Biomedicine; Ca2+-transporting ATPase; Calcium (reticular); Cell Line; Contraction; Endonuclease; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Gene Expression; Human Physiology; Inositol; Insulin; Metabolism; Mice; mRNA stability; Muscle contraction; Muscle Fibers, Skeletal - metabolism; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscles; Musculoskeletal system; Myogenesis; Myotubes; Original Article; Proteolipids - genetics; Proteolipids - metabolism; Ribonucleic acid; RNA; Sarcolipin; Skeletal muscle; Stability analysis; Stresses; Thapsigargin; Thermogenesis; Tunicamycin; Sarcolipin; Myotubes; Endoplasmic reticulum stress; mRNA stability
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/s13105-017-0578-9

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 Ca
2+
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.