Terhzaz, S., Finlayson, A. J., Stirrat, L., Yang, J., Tricoire, H., Woods, D. J., Dow, J. A.T. and Davies, S. A. (2010) Cell-specific inositol 1,4,5 trisphosphate 3-kinase mediates epithelial cell apoptosis in response to oxidative stress in Drosophila. Cellular Signalling, 22(5), pp. 737-748. (doi: 10.1016/j.cellsig.2009.12.009) (PMID:20060894)
Full text not currently available from Enlighten.
Abstract
Organismal stress responses to oxidative stress are relevant to ageing and disease and involve key cell-/tissue -specific signal transduction mechanisms. Using Drosophila, an established in vivo model for stress studies, we show that cell-specific inositol phosphate signaling specifically via Inositol 1,4,5 trisphosphate 3-kinase (InsP3 3-K, IP3K), negatively regulates organismal responses to oxidative stress. We demonstrate that the Drosophila Malpighian tubule (equivalent to vertebrate kidney and liver) is a key epithelial sensor for organismal oxidative stress responses: precise targeting of either gain-of-function constructs of Drosophila IP3Ks (IP3K-1 and IP3K-2), or loss-of-function (RNAi) constructs to only one cell type in tubule reversibly modulates survival of stress-challenged adult flies. In vivo, targeted IP3K-1 directly increases H2O2 production, pro-apoptotic caspase-9 activity and mitochondrial membrane potential. The mitochondrial calcium load in tubule principal cells - assessed by luminescent and fluorescent genetically-encoded mitochondrial calcium reporters - is significantly increased by IP3K-1 under oxidative stress conditions, leading to apoptosis. The Drosophila orthologues of human apoptotic bcl-2 genes include debcl and buffy. Oxidative stress challenge does not modulate gene expression of either debcl or buffy in tubules; and altered debcl expression does not influence survival rates under oxidative stress challenge. Finally, targeted over-expression of either debcl or buffy to tubule principal cells does not impact on tubule caspase-9 activity. Thus, IP3K-1 modulates epithelial cell apoptosis without involvement of bcl-2-type proteins.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dow, Professor Julian and Terhzaz, Dr Selim and Davies, Professor Shireen and Stirrat, Mrs Laura and Yang, Dr Jingli |
| Authors: | Terhzaz, S., Finlayson, A. J., Stirrat, L., Yang, J., Tricoire, H., Woods, D. J., Dow, J. A.T., and Davies, S. A. |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Cellular Signalling |
| Publisher: | Elsevier |
| ISSN: | 0898-6568 |
| ISSN (Online): | 1873-3913 |
| Published Online: | 11 January 2010 |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information