title: Amino acid deprivation disrupts barrier function and induces protective autophagy in intestinal porcine epithelial cells.
abstract: The integrity of intestinal barrier is essential for the absorption of nutrients and health in humans and animals. Dysfunction of the mucosal barrier is associated with increased gut permeability and development of various gastrointestinal diseases. Aside from serving as substrates for protein biosynthesis, amino acids also maintain the health of intestinal mucosal barrier. However, the underlying mechanisms remain unclear. We aimed to determine the effect and mechanism of non-essential amino acid (NEAA) deprivation on intestinal tight junction permeability using porcine intestinal epithelial cells as a model. We found that NEAA deprivation led to an impairment of barrier function as evidenced by increased permeability, decreased trans-epithelial resistance, and decreased expression of tight junction proteins claudin-1 and ZO-1. Importantly, NEAA deprivation induced both apoptosis and autophagy as shown by caspase-3 activation, and poly ADP-ribose polymerase cleavage; and LC3II lipidation and p62 degradation, hallmarks of apoptosis and autophagy, respectively. Importantly, we showed that the autophagy induced by NEAA deprivation counteracts apoptosis. Abrogation of autophagy by 3-methyladenine enhanced NEAA deprivation-induced barrier dysfunction and apoptosis; whereas, activation of autophagy by rapamycin partially rescued NEAA deprivation-induced barrier dysfunction and apoptosis. Taken together, our results demonstrate a critical role of NEAA on the mucosal integrity by regulating cell death and survival signaling pathways.
authors.affiliation: State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, 87131-0001, USA.
authors.forename: Chien-An A
authors.initials: CA
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China. bio2046@hotmail.com.
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000596:Amino Acids / Q000172:deficiency*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D010539:Permeability / Q000187:drug effects*; D015398:Signal Transduction; D013552:Swine
chemical_list: D000596:Amino Acids
keywords: Amino acid deprivation; Apoptosis; Autophagy; Intestinal barrier function