Plasma amino acids imbalance in cirrhotic patients disturbs the tricarboxylic acid cycle of dendritic cell. 2013

Eiji Kakazu, and Yasuteru Kondo, and Takayuki Kogure, and Masashi Ninomiya, and Osamu Kimura, and Yoshiyuki Ueno, and Tooru Shimosegawa
1] Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574 Japan [2] Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo, Aobaku, Sendai, 980-8573 Japan.

An imbalance of plasma amino acids (AA) is observed cirrhotic patients. Here we report that the imbalance suppresses the maturation of dendritic cells (DCs) by reducing the intracellular ATP due to interference with the mitochondrial tricarboxylic acid (TCA) cycle. We used serum-free culture medium consistent with the average concentration of the plasma AA from a healthy volunteer (HCM) and that from patients with advanced cirrhosis (ACM). We compared the function of DCs and the metabolism of glucose-amino acids under each medium. The maturation and intracellular ATP of immature DCs were lower under ACM in spite of the enhancement of mitochondrial respiratory chain complex genes. Metabolomics revealed that the TCA cycle metabolite, fumarate and 2-oxoglutarate were increased in DCs generated under ACM. Consistent with in vitro, In CD1c(+) or CD14(+) cells from cirrhotic patients, the gene expression of 2-oxoglutarate-succinate-fumarate transition enzymes were significantly different from the cells of healthy controls.

UI MeSH Term Description Entries
D008103 Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D002952 Citric Acid Cycle A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds. Krebs Cycle,Tricarboxylic Acid Cycle,Citric Acid Cycles,Cycle, Citric Acid,Cycle, Krebs,Cycle, Tricarboxylic Acid,Cycles, Citric Acid,Cycles, Tricarboxylic Acid,Tricarboxylic Acid Cycles
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D005355 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Cirrhosis,Fibroses
D006521 Hepatitis, Chronic INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors. Chronic Hepatitis,Cryptogenic Chronic Hepatitis,Hepatitis, Chronic, Cryptogenic,Hepatitis, Chronic Active,Hepatitis, Chronic Persistent,Chronic Active Hepatitis,Chronic Hepatitis, Cryptogenic,Chronic Persistent Hepatitides,Chronic Persistent Hepatitis,Hepatitis, Cryptogenic Chronic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino

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