Presenilin promotes dietary copper uptake.
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3646984?pdf=render |
| _version_ | 1818421736498003968 |
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| author | Adam Southon Mark A Greenough George Ganio Ashley I Bush Richard Burke James Camakaris |
| author_facet | Adam Southon Mark A Greenough George Ganio Ashley I Bush Richard Burke James Camakaris |
| author_sort | Adam Southon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T13:15:06Z |
| format | Article |
| id | doaj.art-2d121f1c346242a79eeae9728a0b5428 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T13:15:06Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2d121f1c346242a79eeae9728a0b54282022-12-21T23:00:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6281110.1371/journal.pone.0062811Presenilin promotes dietary copper uptake.Adam SouthonMark A GreenoughGeorge GanioAshley I BushRichard BurkeJames CamakarisDietary 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.http://europepmc.org/articles/PMC3646984?pdf=render |
| spellingShingle | Adam Southon Mark A Greenough George Ganio Ashley I Bush Richard Burke James Camakaris Presenilin promotes dietary copper uptake. PLoS ONE |
| title | Presenilin promotes dietary copper uptake. |
| title_full | Presenilin promotes dietary copper uptake. |
| title_fullStr | Presenilin promotes dietary copper uptake. |
| title_full_unstemmed | Presenilin promotes dietary copper uptake. |
| title_short | Presenilin promotes dietary copper uptake. |
| title_sort | presenilin promotes dietary copper uptake |
| url | http://europepmc.org/articles/PMC3646984?pdf=render |
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