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

Eiji Kakazu, Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Osamu Kimura, Yoshiyuki Ueno, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Article number3459
JournalScientific reports
Volume3
DOIs
Publication statusPublished - 2013 Dec 10

ASJC Scopus subject areas

  • General

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