L -Arginine Availability And Metabolism Is Altered In Ulcerative Colitis

Keywords

amino acids; cationic amino acid transporter; gene expression; inflammatory bowel disease; l -arginine

Abstract

Background: l-arginine (l-Arg) is the substrate for both inducible nitric oxide (NO) synthase (NOS2) and arginase (ARG) enzymes. l-Arg is actively transported into cells by means of cationic amino acid transporter (SLC7) proteins. We have linked l-Arg and arginase 1 activity to epithelial restitution. Our aim was to determine if l-Arg, related amino acids, and metabolic enzymes are altered in ulcerative colitis (UC). Methods: Serum and colonic tissues were prospectively collected from 38 control subjects and 137 UC patients. Dietary intake, histologic injury, and clinical disease activity were assessed. Amino acid levels were measured by high-performance liquid chromatography. Messenger RNA (mRNA) levels were measured by real-time PCR. Colon tissue samples from 12 Crohn's disease patients were obtained for comparison. Results: Dietary intake of arginine and serum l-Arg levels were not different in UC patients versus control subjects. In active UC, tissue l-Arg was decreased, whereas l-citrulline (l-Cit) and the l-Cit/l-Arg ratio were increased. This pattern was also seen when paired involved (left) versus uninvolved (right) colon tissues in UC were assessed. In active UC, SLC7A2 and ARG1 mRNA levels were decreased, whereas ARG2 and NOS2 were increased. Similar alterations in mRNA expression occurred in tissues from Crohn's disease patients. In involved UC, SLC7A2 and ARG1 mRNA levels were decreased, and NOS2 and ARG2 increased, when compared with uninvolved tissues. Conclusions: Patients with UC exhibit diminished tissue l-Arg, likely attributable to decreased cellular uptake and increased consumption by NOS2. These findings combined with decreased ARG1 expression indicate a pattern of dysregulated l-Arg availability and metabolism in UC.

Publication Date

5-31-2016

Publication Title

Inflammatory Bowel Diseases

Volume

22

Issue

8

Number of Pages

1847-1858

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1097/MIB.0000000000000790

Socpus ID

84979927043 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84979927043

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