Carnosine induces intestinal cells to secrete exosomes that activate neuronal cells

PLoS One. 2019 May 28;14(5):e0217394. doi: 10.1371/journal.pone.0217394. eCollection 2019.

Abstract

Recently, we showed that imidazole dipeptide such as carnosine contained abundantly in chicken breast meat improves brain function in a double-blind randomized controlled trial. However, the underlying molecular mechanisms remain unknown. Here, we investigated whether carnosine activates intestinal epithelial cells and induces the secretion of factors that activate brain function. We focused on exosomes derived from intestinal epithelial cells as mediators of brain-gut interaction. Results showed that exosomes derived from Caco-2 cells treated with carnosine significantly induced neurite growth in SH-SY5Y cells. To clarify the molecular basis of this finding, we performed integrated analysis of microRNAs (miRNAs) with altered expression in exosomes in response to carnosine treatment and mRNAs with altered expression in target cells in response to exosome treatment to identify related miRNAs and their target genes. The combination of miR-6769-5p and its target gene ATXN1 was found to be involved in the exosome-induced activation of neuronal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-1 / genetics
  • Brain / drug effects
  • Brain / metabolism
  • Caco-2 Cells
  • Carnosine / pharmacology*
  • Cell Line
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Exosomes / drug effects*
  • Exosomes / genetics
  • Exosomes / metabolism*
  • Gene Expression Profiling
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neurons / metabolism*

Substances

  • ATXN1 protein, human
  • Ataxin-1
  • MicroRNAs
  • Carnosine

Grants and funding

YK awarded JSPS KAKENHI (Japan Society for the Promotion of Science, https://www.jsps.go.jp/, Grant Number: 16K14929). YK received the collaborative research cost from NH Foods Ltd. NH Foods Ltd provided support in the form of salaries for authors [MS, TH], but did not have any additional role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contribution' section.