Biomaterial Database

Energy metabolism disorder mediated ammonia gas-induced autophagy via AMPK/mTOR/ULK1-Beclin1 pathway in chicken livers. 2021

Zhuo Li, and Zhiying Miao, and Linlin Ding, and Xiaohua Teng, and Jun Bao

College of Animal Science and Technology, Northeast Agricultural University, NO. 600 Chang Jiang Road, Xiang Fang District, Harbin 150030, China.

Ammonia gas is a well-known environmental pollution gas, threatening human health. Ammonia gas is also one of the most harmful gases to livestock and poultry for many years. Many studies have demonstrated toxic effect of ammonia gas on animal health, such as eyes, respiratory system, and digestive system. However, the effect of ammonia gas toxicity on chicken livers and underlying molecular mechanism remains unclear. In this study, we selected chicken liver as research object and duplicated successfully ammonia gas poisoning model of chickens. 1-day-old Ross-308 broilers were randomly divided into the control group (the low ammonia gas group), and two treatment groups (the middle ammonia gas group and the high ammonia gas group) (3 replicates per group and 12 chickens per replicate). Ammonia gas concentration in the low ammonia gas group was ≤5 mg/m3 during day 1-42. Ammonia gas concentration in the middle group was set as 10 ± 0.5 mg/m3 during day 1-21, and 15 ± 0.5 mg/m3 during day 22-42). Ammonia gas concentration in the high ammonia gas group was set as 20 ± 0.5 mg/m3 during day 1-21, and 45 ± 0.5 mg/m3 during day 22-42. The ultrastructure of chicken livers was observed. The activities of four ATPases (Na+K+-ATPase, Mg++-ATPase, Ca++-ATPase, and Ca++Mg++-ATPase), the expression of twelve energy metabolism-related genes (HK1, HK2, PK, PFK, PDHX, CS, LDHA, LDHB, SDHA, SDHB, avUCP, and AMPK), as well as the expression of ten autophagy-related genes (PI3K, LC3I, LC3II, Beclin1, SQSTM1, mTOR, ULK1, ATG5, ATG12, and ATG13) were measured to explore the effect of ammonia gas on energy metabolism and autophagy in chicken livers. Our results showed that excess ammonia gas induced mitochondrial and autophagic damage in chicken liver tissue cells. Meanwhile, ATPases activities were inhibited and the expression of energy metabolism-related genes changed during ammonia gas treatment, meaning that excess ammonia gas caused energy metabolism disorder. Furthermore, ammonia gas exposure altered the expression of autophagy-related genes, suggesting that ammonia gas treatment caused autophagy in chicken livers. Moreover, ammonia gas-induced AMPK compensatory up-regulation activated autophagy process through inhibiting mTOR and promoting ULK1. In addition. there were dose-dependent and time-dependent effects on all detected indexes in ammonia gas-caused chicken liver cell damage. Taken together, AMPK/mTOR/ULK1-Beclin1 pathway participated in energy metabolism disorder-mediated autophagic injury caused by ammonia gas exposure in chicken livers.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D002645	Chickens	Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.	Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D004734	Energy Metabolism	The chemical reactions involved in the production and utilization of various forms of energy in cells.	Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071186	Beclin-1	An autophagy related protein which functions as a core subunit of PHOSPHATIDYLINOSITOL 3-KINASE MULTIPROTEIN COMPLEXES. It mediates the formation of phosphatidylinositol 3-phosphate and functions in AUTOPHAGY, where it is required for maturation of the AUTOPHAGOSOME. It also functions in ENDOCYTOSIS and CYTOKINESIS as part of a separate complex. Beclin-1 associates with INTRACELLULAR MEMBRANES and interacts with the PROTO-ONCOGENE PROTEINS C-BCL-2 and BCL-X PROTEIN.	ATG-6 Protein,ATG6 Protein,Beclin-1 Protein,Beclin1,Coiled-coil Myosin-like Bcl2-interacting Protein,GT197 Protein,ATG 6 Protein,Beclin 1,Beclin 1 Protein,Coiled coil Myosin like Bcl2 interacting Protein
D000071189	Autophagy-Related Protein-1 Homolog	A serine/threonine-protein kinase that functions in AUTOPHAGY in response to starvation. It acts on the PHOSPHATIDYLINOSITOL 3-KINASE complex PIK3C3 to regulate AUTOPHAGOSOME formation. It also functions as both a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) and is activated by AMPK, which it also negatively regulates.	Serine-Threonine Protein Kinase ULK1,ULK1 Protein,Unc-51 Like Autophagy Activating Kinase 1,Unc-51-Like Kinase 1,Autophagy Related Protein 1 Homolog,Serine Threonine Protein Kinase ULK1,Unc 51 Like Autophagy Activating Kinase 1,Unc 51 Like Kinase 1
D000641	Ammonia	A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001343	Autophagy	The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer.	Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy