Yeast β-glucan alleviates the subacute rumen acidosis-induced mitochondrial dysfunction and cell structure integrity injury in yak rumen epithelial cells via the TLR2/PI3K/mTOR signaling pathway.

Subacute rumen acidosis (SARA) is characterized by decreased rumen fluid pH and impaired rumen epithelial function. In this study, the underlying molecular mechanisms of β-glucan can alleviate SARA induced damage to yak rumen epithelial cells (YRECs), and its potential protective effects were investigated. The results demonstrated that β-glucan alleviated the decrease in cell viability and LDH release induced by SARA. Furthermore, SARA led to mitochondrial dysfunction, including disrupted mitochondrial morphology observed through fluorescence and transmission electron microscopy, decreased mitochondrial membrane potential and ATP levels, increased intracellular Ca2+ and reactive oxygen species levels, reduced activity of glutathione metabolism-related enzymes in the antioxidant system, and inhibited expression of oxidative phosphorylation-related genes and proteins. Additionally, SARA disrupted the expression of cell cytoskeleton and cell junction genes and proteins. Meanwhile, SARA induced a cellular inflammatory response, inhibited ion channel transport, activated acid-sensitive receptors, and disrupted intracellular acid-base balance. The cells were pre-treatment with β-glucan significantly mitigated these adverse effects, maintaining normal cellular functions. The specific inhibitors Dactolisib and rapamycin, which target and inhibit the PI3K/mTOR signaling pathway, reversed the effects of β-glucan in regulating the impact of SARA on the signaling pathway. The downstream mTOR signaling pathway inhibitor rapamycin reversed the effects of β-glucan in mitigating SARA-induced disruptions in mitochondrial and cell cytoskeleton functions. In conclusion, in vitro findings suggest that yeast β-glucan potentially regulates SARA-induced effects on mitochondrial function, cell cytoskeleton, and cell junctions by inhibiting acid-sensitive receptors and activating TLR2/PI3K/mTOR signaling pathway.