Crosstalk of JNK1-STAT3 is critical for RAW264.7 cell survival.

Abstract

T-2 toxin, a major compound of trichothecenes, inhibits protein synthesis and induces inflammation and cell apoptosis through the activation of MAPK pathway. The JAK/STAT pathway has recently been shown to be downstream targets of trichothecenes. However, whether there is any crosstalk between JNK and JAK/STAT pathways in trichothecene toxicity has not been studied. In the present study, we explored this potential in RAW264.7 cells treated with T-2 toxin. Our results revealed a crosstalk between JNK1 and STAT3 after T-2 toxin treatment, which was mediated by K-Ras. T-2 toxin treatment resulted in rapid phosphorylation, and more importantly, JNK1-STAT3 signaling pathway was shown to maintain the normal function of the mitochondria and to inhibit T-2 toxin-induced apoptosis. Therefore, this pathway was considered to be a potential cell survival pathway. Breakdown and degranulation of ribosomes in the rough endoplasmic reticulum and swelling of mitochondria were clearly visible after the cells had been incubated with T-2 toxin for 12h. Our data suggest that T-2 toxin had a Janus face: it induced both apoptotic and cell survival pathways. These results suggest that the crosstalk and the balance between MAPK and JAK/STAT pathway might be involved in T-2 toxin-induced apoptosis in RAW264.7 cells.

• Authors: Qinghua Wu, Xu Wang, Dan Wan, Juan Li, Zonghui Yuan
• Journal: Cellular signalling (Cell Signal) Vol. 26 Issue 12 Pg. 2951-60 (Dec 2014) ISSN: 1873-3913 [Electronic] England
• PMID: 25269780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Anthracenes
• Cytokines
• STAT3 Transcription Factor
• pyrazolanthrone
• Janus Kinases
• Mitogen-Activated Protein Kinase 8
• ras Proteins
• T-2 Toxin

Topics

• Animals
• Anthracenes (pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Cytokines (genetics, metabolism)
• Fluorescent Antibody Technique
• Gene Expression Regulation (drug effects)
• Janus Kinases (metabolism)
• Kinetics
• Macrophages (cytology, drug effects, metabolism, ultrastructure)
• Mice
• Mitochondria (drug effects, metabolism, ultrastructure)
• Mitogen-Activated Protein Kinase 8 (metabolism)
• Models, Biological
• Phosphorylation (drug effects)
• Ribosomes (drug effects, metabolism, ultrastructure)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• T-2 Toxin (pharmacology)
• ras Proteins (metabolism)