Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12 myotubes
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ORIGINAL ARTICLE
Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12 myotubes Nobuhiko Takahashi 1,2 & Atsushi P. Kimura 3 & Sumiyoshi Naito 4 & Mika Yoshida 4 & Osamu Kumano 5 & Takeshi Suzuki 5 & Satoshi Itaya 2 & Mitsuru Moriya 2 & Masahiro Tsuji 2 & Masahiro Ieko 1,2
Received: 23 January 2017 / Accepted: 29 June 2017 # University of Navarra 2017
Abstract 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 * Nobuhiko Takahashi [email protected]
1
Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0023, Japan
2
Department of Internal Medicine, Health Sciences University of Hokkaido Hospital, 2-5 Ainosato, Kita-ku, Sapporo, Hokkaido 002-8072, Japan
3
Department of Biological Sciences, Faculty of Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan
4
Division of Clinical Laboratory, Health Sciences University of Hokkaido Hospital, 2-5 Ainosato, Kita-ku, Sapporo, Hokkaido 002-8072, Japan
5
Sysmex Corporation, 4-4-4 Takatsukadai, Kobe, Hyogo 651-2271, Japan
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. Keywords Sarcolipin . Myotubes . Endoplasmic reticulum stress . mRNA stability
Introduction Sarcolipin is a 31 amino acid transmembrane protein mainly expressed in skeletal and cardiac atria muscles [4, 33]. In skeletal muscle cells, sarcolipin is present in the sarco/ endoplasmic reticulum, and interacts with sarco/endoplasmic reticulum calcium ion (Ca2+) ATPase (SERCA) [15]. SERCA is responsible for transporting Ca2+ from the cytosol into the lumen of the sarco/endoplasmic reticulum by hydrolyzing ATP following muscular contraction. When sarcolipin interacts with SERCA, SERCA produces heat instead of Ca2+ transport by hydrolyzing ATP [5, 9]. Indeed, seve
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