Dying enterocytes downregulate signaling pathways converging on Ras: rescue by protease inhibition
| Autor: | Wendi Gardner, Wen Hui Jin, Lawrence A. Scheving, Kang-Mei Chong, Frederick O. Cope |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Programmed cell death Physiology Cell Son of Sevenless Apoptosis Mice Inbred Strains Mice Organ Culture Techniques Intestine Small medicine Animals Protease Inhibitors RNA Messenger Growth Substances Cells Cultured Caspase biology Histocytochemistry DNA Cell Biology Cysteine protease Cell biology medicine.anatomical_structure Genetic Techniques Biochemistry Cell culture ras Proteins biology.protein Tumor Suppressor Protein p53 Signal transduction Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 274:C1363-C1372 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1998.274.5.c1363 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|