Related Experiment Videos
Double-stranded RNA activates a p38 MAPK-dependent cell survival program in biliary epithelia
Laura Tadlock1, Yoko Yamagiwa, Carla Marienfeld
1Scott and White Clinic, Texas A&M University System Health Science Center, College of Medicine, Temple, Texas 76508, USA.
Summary
Double-stranded RNA (dsRNA) activates a cell-survival pathway in biliary cells. This p38 MAPK-dependent pathway may influence responses to viral infections or DNA damage.
Area of Science:
- Cell Biology
- Molecular Biology
- Hepatology
Background:
- Double-stranded RNA (dsRNA) is generated during viral replication and genotoxic stress.
- Understanding cellular responses to dsRNA in biliary epithelia is crucial for comprehending the effects of DNA damage and viral infections.
Purpose of the Study:
- To investigate the impact of dsRNA on biliary epithelial cell proliferation and apoptosis.
- To elucidate the role of the stress-activated p38 MAPK signaling pathway in dsRNA-mediated cellular responses.
Main Methods:
- Treatment of Mz-ChA-1 human malignant cholangiocytes with dsRNA.
- Assessment of cell proliferation, apoptosis, and caspase activity.
- Analysis of MAPK signaling pathway activation (p38 MAPK, JNK, MEK1/2) and protein kinase R phosphorylation.
- Pharmacological inhibition of p38 MAPK using SB-203580.
Main Results:
- dsRNA did not induce apoptosis or proliferation in cholangiocytes.
- dsRNA reduced cytotoxicity from camptothecin and TNF-related apoptosis-inducing ligand.
- dsRNA decreased caspase 3, 8, and 9 activities.
- dsRNA enhanced phosphorylation of p38 MAPK and JNK, but not MEK1/2 or protein kinase R.
- Inhibition of p38 MAPK increased basal caspase activity.
Conclusions:
- dsRNA activates a p38 MAPK-dependent cell-survival pathway in biliary epithelial cells.
- This pathway may modulate the biliary epithelium's response to dsRNA from genotoxic injury or viral infections.