Presenilin promotes dietary copper uptake
| Autor: | George Ganio, James Camakaris, Richard Burke, Mark Greenough, Adam Southon, Ashley I. Bush |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Anatomy and Physiology
SOD1 lcsh:Medicine medicine.disease_cause Biochemistry Presenilin Superoxide dismutase Molecular Genetics Superoxide Dismutase-1 Model Organisms RNA interference Molecular Cell Biology mental disorders medicine Genetics Animals Homeostasis lcsh:Science Biology Conserved Sequence Cellular Stress Responses Gene knockdown Multidisciplinary biology Superoxide Dismutase Drosophila Melanogaster fungi lcsh:R Presenilins Midgut Biological Transport Animal Models biology.organism_classification Diet nervous system diseases Oxidative Stress Metabolism Gene Knockdown Techniques biology.protein Insect Proteins RNA Interference lcsh:Q Drosophila melanogaster Physiological Processes Digestive System Oxidative stress Copper Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 5, p e62811 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Dietary copper is essential for multicellular organisms. Copper is redox active and required as a cofactor for enzymes such as the antioxidant Superoxide Dismutase 1 (SOD1). Copper dyshomeostasis has been implicated in Alzheimer’s disease. Mutations in the presenilin genes encoding PS1 and PS2 are major causes of early-onset familial Alzheimer’s disease. PS1 and PS2 are required for efficient copper uptake in mammalian systems. Here we demonstrate a conserved role for presenilin in dietary copper uptake in the fly Drosophila melanogaster. Ubiquitous RNA interference-mediated knockdown of the single Drosophila presenilin (PSN) gene is lethal. However, PSN knockdown in the midgut produces viable flies. These flies have reduced copper levels and are more tolerant to excess dietary copper. Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake. SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat. These data support presenilin being needed for dietary copper uptake in the gut and so impacting on SOD activity and tolerance to oxidative stress. These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|