Taurine attenuates gossypol-induced apoptosis of C2C12 mouse myoblasts via the GPR87-AMPK/AKT signaling
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ORIGINAL ARTICLE
Taurine attenuates gossypol‑induced apoptosis of C2C12 mouse myoblasts via the GPR87‑AMPK/AKT signaling Mengmeng Yu1 · Yang Wang1 · Ping Li1 · Meng Li1 · Xuejun Gao1 Received: 9 November 2019 / Accepted: 5 September 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Gossypol, a toxic polyphenol extracted from cotton seeds, is hazardous to human and animal health. Taurine is considered as an essential or semi-essential amino acid and has diverse cytoprotective effects. This study was aimed to investigate the protective effect and molecular mechanism of taurine against apoptosis of C2C12 mouse myoblasts induced by gossypol. C2C12 mouse myoblasts were exposed to gossypol (0, 1 nM, 10 nM, 100 nM, 1 μM, and 10 μM). Cell numbers were rapidly decreased with increasing concentrations of gossypol. Gossypol significantly induced apoptosis, decreased Bcl2 expression, and increased the protein levels of Bax and the cleaved caspase 3. Taurine (0.24 mM) treatment largely rescued the cell number decreased by gossypol, attenuated gossypol-induced cell apoptosis. GPR87 knockdown abolished the inhibition by taurine of cell apoptosis. Furthermore, GPR87 overexpression attenuated cell apoptosis induced by gossypol. Both taurine treatment and GPR87 overexpression stimulated AKT phosphorylation but inhibited AMPK phosphorylation, whereas gossypol had the opposite effects. Taurine treatment promoted GPR87 expression and subcellular localization and partially rescued the inhibition of gossypol on this expression. In summary, these data reveal that taurine attenuates gossypol-induced apoptosis of C2C12 mouse myoblasts via the GPR87-AMPK/AKT signaling. Keywords Apoptosis · C2C12 mouse myoblasts · Gossypol · GPR87 · Taurine Abbreviations AKT Protein kinase B AMPK Adenosine 5′-monophosphate (AMP)-activated protein kinase Bax Bcl-2-associated X protein Bcl-2 B-cell lymphoma 2 DAPI 4′,6-Diamidino-2-phenylindole GPR87 G protein-coupled receptor 87 mTOR The mechanistic target of rapamycin PI3K Phosphoinositide 3-kinase
Handling Editor: S. W. Schaffer. * Xuejun Gao [email protected] 1
College of Animal Science, Yangtze University, Jingzhou 434020, China
Introduction Gossypol, a toxic polyphenol extracted from cotton seeds, is hazardous to human and animal health (Lim et al. 2019; Lin et al. 2016). Gossypol also has therapeutic potential, exhibiting anticancer, antifertility, antiinflammatory, and antimicrobial properties (Keshmiri-Neghab and Goliaei 2014; Lu et al. 2017a, b; Zeng et al. 2019). Previous reports have demonstrated that gossypol can inhibit cell proliferation and induce cell apoptosis. Gossypol can decrease the expression of B-cell lymphoma 2 (Bcl2), increase the expression of Bcl2-associated X protein (Bax) and activation of caspase-3, leading to cell apoptosis (Wang et al. 2018; Lu et al. 2017a, b; Liang et al. 2018). Cottonseed meal is used as a nutrient in animal feeding, however, the toxicity of gossypol limits its use in animal production (Gadelha et al. 2014; Moretti e
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