title: Plasma amino acids imbalance in cirrhotic patients disturbs the tricarboxylic acid cycle of dendritic cell.
abstract: 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.
authors: 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.
authors: Eiji
authors: E
authors: Kakazu
authors: Yasuteru
authors: Y
authors: Kondo
authors: Takayuki
authors: T
authors: Kogure
authors: Masashi
authors: M
authors: Ninomiya
authors: Osamu
authors: O
authors: Kimura
authors: Yoshiyuki
authors: Y
authors: Ueno
authors: Tooru
authors: T
authors: Shimosegawa
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000097:blood*; D002952:Citric Acid Cycle; D003713:Dendritic Cells / Q000378:metabolism*; D005355:Fibrosis / Q000097:blood / Q000378:metabolism*; D015870:Gene Expression; D006521:Hepatitis, Chronic / Q000097:blood / Q000378:metabolism / Q000473:pathology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D009000:Monocytes / Q000378:metabolism; D010641:Phenotype; D012720:Severity of Illness Index; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000255:Adenosine Triphosphate; D058570:TOR Serine-Threonine Kinases