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Combination Metabolomics Approach for Identifying Endogenous Substrates of Carnitine/Organic Cation Transporter OCTN1

Yusuke Masuo1, Yuri Ohba1, Kohei Yamada1

  • 1Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.

Pharmaceutical Research
|October 4, 2018
PubMed
Abstract

Insights

Researchers identified spermine as an endogenous substrate of the carnitine/organic cation transporter OCTN1. This finding links OCTN1 to gastrointestinal inflammation and provides a novel tool for substrate identification.

Area of Science:

  • Biochemistry
  • Genetics
  • Immunology

Background:

  • Solute carrier SLC22A4 encodes the carnitine/organic cation transporter OCTN1.
  • OCTN1 is associated with inflammatory bowel disease (IBD), but its role in pathogenesis is unclear.

Purpose of the Study:

  • To identify endogenous substrates of OCTN1 linked to gastrointestinal inflammation.
  • To investigate the role of OCTN1 in IBD pathogenesis.

Main Methods:

  • Utilized HEK293/OCTN1 and mock cells incubated with colon extracts from colitis-induced mice.
  • Employed 3-aminopyridyl-N-hydroxysuccinimidyl carbamate (APDS) for selective labeling of OCTN1 substrates.
  • Applied precursor ion scanning to identify candidate OCTN1 substrates.

Main Results:

  • Identified spermine as an OCTN1 substrate using a combination metabolomics approach.
  • Observed significantly lower spermine concentration in peripheral blood mononuclear cells of octn1 gene knockout mice.
  • Found reduced inflammatory cytokine gene expression in peritoneal macrophages from octn1 knockout mice.

Conclusions:

  • The developed metabolomics approach is a novel tool for identifying endogenous OCTN1 substrates.
  • Spermine is a potential endogenous substrate of OCTN1 involved in gastrointestinal inflammation.
Keywords:
Crohn’s diseaseOCTN1endogenous substratesmetabolomicstransporter

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