Selenomethionine activates selenoprotein S, suppresses Fas/FasL and the mitochondrial pathway, and reduces Escherichia coli- induced apoptosis of bovine mammary epithelial cells

Escherichia coli is a major environmental pathogen causing bovine mastitis, characterized by cell death and mammary tissue damage. Apoptosis, a form of cell death, has an important role in the pathogenesis of mastitis. Selenium, an essential trace element, protects against mastitis by acting through several biochemical pathways, potentially including prevention of apoptosis. Our objective was to investigate whether selenomethionine (SeMet) attenuated E. coli-induced apoptosis in bovine mammary epithelial cells (bMEC). These cells were cultured in vitro and treated with 0, 5, 10, 20, and 40 mu M SeMet for 12 h, with or without E. coli (multiplicity of infection of 5) for 8 h. Treatment with SeMet/Z-IE(OMe)TD(OMe)-FMK (ZIK)/Z-LE(OMe) HD(OMe)-FMK (ZLK, specific inhibitors of caspase-8 and-9, respectively) significantly counteracted effects of E. coli on bMEC. Specifically, SeMet upregulated selenoprotein S (SeS) and increased mitochondrial membrane potential and the ratio of Bcl-2 and Bax. Furthermore, it decreased protein expressions of Fas, FasL, FADD, cleaved caspase-8, cytochrome c, cleaved caspase-9, and cleaved caspase-3, namely, decreasing protein expression of the Fas/FasL and mitochondrial pathways. Furthermore, it downregulated total apoptosis indexes in E. coli-infected bMEC. Although ZIK and ZLK (specific inhibitors of caspases 8 and 9, respectively) significantly inhibited Fas/FasL and the mitochondrial apoptotic pathway and apoptosis indexes, respectively, substantial apoptosis still occurred. In conclusion, SeMet attenuated E. coli-induced apoptosis in bMEC by activating SeS, associated with Fas/FasL and mitochondrial pathways.

Automated summary

SeMet attenuated E. coli-induced apoptosis in bMEC by activating SeS, associated with Fas/FasL and mitochondrial pathways.