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Updated: Jul 27, 2026
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
Summary
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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