Specific inhibitory effects of exogenous d-Aspartate on the proliferation of intestinal epithelial cells

Biochem Biophys Res Commun. 2024 Nov 19:734:150659. doi: 10.1016/j.bbrc.2024.150659. Epub 2024 Sep 5.

Abstract

d-amino acids have been actively examined since improved analytical techniques revealed their presence in animal bodies. Although D-Asp was identified in mammals earlier than D-Ser, research on D-Asp has lagged behind that on D-Ser, mainly because the target protein of D-Asp remains unknown. To date, the only reported functions of D-Asp are its roles in reproduction and suggested neuromodulatory functions. Since d-amino acids are also present in food, it is important to clarify their effects on gastrointestinal epithelial cells, which are always contacted after ingestion. Therefore, the present study examined the effects of d-amino acids on gastrointestinal tract basal cells. The effects of 11 types of amino acids (Ala, Arg, Asn, Asp, Gln, Glu, Leu, Lys, Pro, Ser, and Val) on the proliferation of three types of gastrointestinal epithelial cells (HGC-27, IEC-6, and Caco-2) were assessed. Although the proliferation of HGC-27 and Caco-2 was not affected by any of the 11 types of L- and d-amino acids, D-Asp inhibited the proliferation of IEC-6, derived from small intestinal epithelial cells, in concentration- and exposure time-dependent manners. The present study also examined uptake transporters, metabolic enzymes, and insulin signaling pathways; however, the mechanisms underlying the inhibitory effects of D-Asp on the proliferation of IEC-6 were not elucidated. A more detailed understanding of these mechanisms may lead to the development of pharmaceuticals as main drugs or formulation materials. Further studies are warranted on the physiological effects of d-amino acids, including D-Asp.

Keywords: Aspartate; Glutamine transporter; Intestinal epithelial cell; Proliferation suppression; d-amino acid.

MeSH terms

  • Animals
  • Aspartic Acid / metabolism
  • Aspartic Acid / pharmacology
  • Caco-2 Cells
  • Cell Line
  • Cell Proliferation* / drug effects
  • D-Aspartic Acid / metabolism
  • D-Aspartic Acid / pharmacology
  • Epithelial Cells* / cytology
  • Epithelial Cells* / drug effects
  • Epithelial Cells* / metabolism
  • Humans
  • Intestinal Mucosa* / cytology
  • Intestinal Mucosa* / drug effects
  • Intestinal Mucosa* / metabolism
  • Rats

Substances

  • D-Aspartic Acid
  • Aspartic Acid