Glycine represses endoplasmic reticulum stress-related apoptosis and improves intestinal barrier by activating mammalian target of rapamycin complex 1 signaling

ABSTRACT Endoplasmic reticulum (ER) stress has been associated with the dysfunction of intestinal barrier in humans and animals. We have previously shown that oral administration of glycine to suckling-piglets improves ER stress-related intestinal mucosal barrier impairment and jejunal epithelial apoptosis. However, the underlying mechanism remains unknown. In this study, the protective effect and the mechanism of glycine on apoptosis and dysfunction in intestinal barrier induced by brefeldin A (BFA), an ER stress inducer, was explored in porcine intestinal epithelial cells (IPEC-1). The results showed that BFA treatment led to enhanced apoptosis and upregulation of proteins involved in ER stress signaling, including inositol-requiring enzyme 1α (IRE1α), activating transcription factor 6α (ATF6α), c-Jun N-terminal kinase (JNK), and C/EBP-homologous protein (CHOP). In addition, BFA induced a dysfunction in intestinal epithelial barrier, as evidenced by the increased paracellular permeability, decreased transepithelial electrical resistance (TEER), and reduced abundance of tight junction proteins (occludin, claudin-1, zonula occludens [ZO]-1, and ZO-2). These alterations triggered by BFA were significantly abolished by glycine treatment (P