Dying enterocytes downregulate signaling pathways converging on Ras: rescue by protease inhibition. Academic Article uri icon

Overview

abstract

  • Organ and cell cultures of the small intestine serve as excellent in vitro models for programmed cell death (PCD). Cells cultured in serum-free, minimal medium rapidly died, as evidenced by histological changes, internucleosomal DNA cleavage, and TdT-mediated dUTP nick end labeling. Cell death was pervasive, although nonepithelial cells within the fibrovascular villus core were spared. PCD did not require a functional p53 gene. Serine and cysteine protease inhibitors, but not FCS, suppressed it. Relative to structural and functional proteins, dying enterocytes rapidly downregulated Ras-convergent proteins, including epidermal growth factor receptor, Erb-B2, and the son of sevenless guanine nucleotide exchangers. Reductions in the steady-state levels of both protein and mRNA were observed. These reductions were prevented by a combination of death-defying serine and caspase inhibitors, indicating a requirement for the initiation of death. Thus, during catastrophic PCD, intestinal epithelial cells delete cell surface signaling pathways responsible for Ras activation.

publication date

  • May 1, 1998

Research

keywords

  • Apoptosis
  • Intestine, Small
  • Protease Inhibitors
  • Signal Transduction
  • ras Proteins

Identity

Scopus Document Identifier

  • 0031833278

Digital Object Identifier (DOI)

  • 10.1152/ajpcell.1998.274.5.C1363

PubMed ID

  • 9612224

Additional Document Info

volume

  • 274

issue

  • 5