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Updated: Jul 27, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Dying enterocytes downregulate signaling pathways converging on Ras: rescue by protease inhibition

L A Scheving1, W H Jin, K M Chong

  • 1Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

The American Journal of Physiology
|June 5, 1998
PubMed

Insights

Small intestinal cells rapidly undergo programmed cell death (PCD) in culture. This process involves downregulating Ras-signaling proteins, crucial for cell survival.

Area of Science:

  • Cell Biology
  • Gastroenterology
  • Molecular Biology

Background:

  • Organ and cell cultures of the small intestine are valuable in vitro models for studying programmed cell death (PCD).
  • Understanding the mechanisms of intestinal cell death is crucial for gastrointestinal health and disease.

Purpose of the Study:

  • To investigate the mechanisms of programmed cell death (PCD) in cultured intestinal epithelial cells.
  • To identify key molecular pathways involved in intestinal cell death.

Main Methods:

  • Utilized organ and cell cultures of the small intestine.
  • Assessed cell death through histological changes, DNA fragmentation, and TdT-mediated dUTP nick end labeling.
  • Analyzed protein and mRNA levels of Ras-convergent proteins using inhibitors of proteases and caspases.

Main Results:

  • Cells cultured in serum-free medium exhibited rapid PCD, independent of a functional p53 gene.
  • Serine and cysteine protease inhibitors suppressed cell death.
  • Dying enterocytes showed rapid downregulation of Ras-convergent proteins (e.g., EGFR, Erb-B2, SOS) at both protein and mRNA levels.
  • Inhibitors of serine and caspase proteases prevented these reductions, confirming a requirement for death initiation.

Conclusions:

  • Programmed cell death (PCD) in intestinal epithelial cells is a rapid process involving the downregulation of cell surface signaling pathways essential for Ras activation.
  • This study elucidates key molecular events during intestinal cell death, offering insights into potential therapeutic targets.

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