• Mol Med Rep · Oct 2017

    SERCA1 attenuates diaphragm relaxation and uptake rate of SERCA in rats with acute sepsis.

    • Jianyou Zhang, Hui Liu, Shitong Li, Jin Wu, and Jianhong Sun.
    • Department of Anesthesiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China.
    • Mol Med Rep. 2017 Oct 1; 16 (4): 5015-5022.

    AbstractThe present study aimed to investigate the effects of acute sepsis on diaphragm contractility and relaxation, via examining the Ca2+‑uptake function of sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA), and the protein levels of SERCA1, SERCA2 and the ryanodine receptor (RyR) of the sarcoplasmic reticulum (SR). A sepsis rat model was established through cecal ligation and puncture (CLP). A total of 6 and 12 h following CLP, the isometric contractile and relaxation parameters of the diaphragm were measured. In addition, Ca2+ uptake and release from the SR, and the protein expression levels of SERCA1, SERCA2 and RyR in diaphragm muscle tissue were investigated. At 6 and 12 h post‑CLP, the diaphragm half‑relaxation time was prolonged and the maximum rate of tension decline was decreased and the Ca2+‑uptake function of SERCA was markedly reduced. The maximum rate of twitch force development, the maximal twitch and tetanic tension, and the release function of SR were decreased at 12 h post‑CLP. A total of 12 h following CLP, the protein expression levels of SERCA1 were significantly downregulated, and its activity was significantly reduced; conversely, the protein levels of SERCA2 remained unaltered. The present findings indicated that at the acute stage of sepsis induced by CLP the contractile and relaxation functions of the diaphragm were significantly compromised. The impairments in relaxation may be a result of the impaired uptake function of the SR and the downregulation in SERCA1 protein expression. Conversely, the compromised contractility may be a result of the impaired release function of the SR and the downregulation in RyR protein levels. This could provide some new insights into the treatment of sepsis. In acute stages of sepsis, the improvement of SERCA function could reduce the disequilibrium of calcium homeostasis to improve the critical illness myopathy and respiratory failure.

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