Human Gsta1-1 Reduces C-jun N-terminal Kinase Signalling and Apoptosis in Caco-2 Cells.
From: Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1.
The Biochemical journal
- Publish Date: Nov 2006
- ISSN: 1470-8728
- Volume: 400
- Issue: 1
- Pages: 135-41
- Medium: Internet
- Language: English
- Citation (JAMA): Romero Laura, Andrews Kimberly, Ng Lorraine, et al. Human Gsta1-1 Reduces C-jun N-terminal Kinase Signalling and Apoptosis in Caco-2 Cells.. Biochem. J. Nov 2006;400:135-41
Abstract
The effect of GSTA1-1 (glutathione S-transferase Alpha 1-1) on JNK (c-Jun N-terminal kinase) activation was investigated in Caco-2 cells in which GSTA1 expression increases with degree of confluency, and in MEF3T3 cells with Tet-Off-inducible GSTA1 expression. Comparison of GSTA1 expression in pre-confluent, confluent and 8-day post-confluent Caco-2 cells revealed progressively increasing mRNA and protein levels at later stages of confluency. Exposure of pre-confluent cells to stress conditions including IL-1beta (interleukin-1beta), H2O2 or UV irradiation resulted in marked increases in JNK activity as indicated by c-Jun phosphorylation. However, JNK activation was significantly reduced in post-confluent cells exposed to the same stresses. Western-blot analysis of GSTA1-1 protein bound to JNK protein pulled down from cellular extracts showed approx. 4-fold higher GSTA1-1-JNK complex formation in post-confluent cells compared with pre-confluent cells. However, stress conditions did not alter the amount of GSTA1-1 bound to JNK. The role of GSTA1-1 in JNK suppression was more specifically revealed in Tet-Off-inducible MEF3T3-GSTA1-1 cells in which GSTA1 overexpression significantly reduced phosphorylation of c-Jun following exposure to IL-1beta, H2O2 and UV irradiation. Finally, the incidence of tumour necrosis factor alpha/butyrate-induced apoptosis was significantly higher in pre-confluent Caco-2 cells expressing low levels of GSTA1 compared with post-confluent cells. These results indicate that GSTA1 suppresses activation of JNK signalling by a pro-inflammatory cytokine and oxidative stress and suggests a protective role for GSTA1-1 in JNK-associated apoptosis.
Mesh Headings (Keywords): 3T3 Cells, Animals, Apoptosis, Blotting, Western, Butyrates, Caco-2 Cells, Enzyme Activation, Gene Expression Regulation, Enzymologic, Glutathione Transferase, Humans, Hydrogen Peroxide, In Situ Nick-End Labeling, Interleukin-1beta, Isoenzymes, JNK Mitogen-Activated Protein Kinases, Mice, Phosphorylation, Protein Binding, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Time Factors, Tumor Necrosis Factor-alpha
Check for Full Text / PubMed Unique Identifier (PMID): 16836488
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